Adoptive Immunotherapy for Infection Control Using Antigen-Specific Donor-Derived T Cells After Transplantation

  • Hermann Einsele
  • Götz-Ulrich Grigoleit
  • Stephan Mielke
Chapter

Abstract

Over the decades both autologous and allogeneic cellular immunotherapy have evolved to a standard treatment option for several malignant and non-malignant disorders offering long-term disease control or even cure in the majority of cases. However, infectious complications as a result of an immunosuppressive environment or missing or dysfunctional cellular effectors leave infectious complications as one of the most important challenges. Here, we present the underlying mechanisms leading to these complications and discuss novel cellular strategies to overcome in particular infectious complications of viral (CMV, EBV, HSV, and HHV6) and fungal (Candida and Aspergillus) origin by harnessing the effects of adoptive immunotherapy. Taking both technical aspects of selection and culturing methods as well as functional aspects of the different cellular compartments such as central or effector memory or gamma–delta T lymphocytes into account we provide an overview of where adoptive immunotherapy stands to today in light of the most recent pharmaceutical developments.

Keywords

AlloSCT Adoptive immunotherapy CMV EBV Adenovirus fungal infection Aspergillus 

References

  1. 1.
    Whimbey E, Elting LS, Couch RB, et al. Influenza A virus infections among hospitalized adult bone marrow transplant recipients. Bone Marrow Transplant. 1994;13:437–40.PubMedGoogle Scholar
  2. 2.
    Lewis VA, Champlin R, Englund J, et al. Respiratory disease due to parainfluenza virus in adult bone marrow transplant recipients. Clin Infect Dis. 1996;23:1033–7.PubMedCrossRefGoogle Scholar
  3. 3.
    Nichols WG, Corey L, Gooley T, et al. Parainfluenza virus infections after hematopoietic stem cell transplantation: risk factors, response to antiviral therapy, and effect on transplant outcome. Blood. 2001;98:573–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Whimbey E, Champlin RE, Couch RB, et al. Community respiratory virus infections among hospitalized adult bone marrow transplant recipients. Clin Infect Dis. 1996;22:778–82.PubMedCrossRefGoogle Scholar
  5. 5.
    Ljungman P, Gleaves CA, Meyers JD. Respiratory virus infection in immunocompromised patients. Bone Marrow Transplant. 1989;4:35–40.PubMedGoogle Scholar
  6. 6.
    Ada GL, Jones PD. The immune response to influenza infection. Curr Top Microbiol Immunol. 1986;128:1–54.PubMedCrossRefGoogle Scholar
  7. 7.
    Cannon MJ, Openshaw PJ, Askonas BA. Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus. J Exp Med. 1988;168:1163–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Bowden RA, Sayers M, Flournoy N, et al. Cytomegalovirus immune globulin and seronegative blood products to prevent primary cytomegalovirus infection after marrow transplantation. N Engl J Med. 1986;314:1006–10.PubMedCrossRefGoogle Scholar
  9. 9.
    Meyers JD. Infections in marrow transplant recipients. In: Mandell GL, Douglas Jr RG, Bennett JE, editors. Principles and practices of infectious diseases. New York: Churchill Livingstone; 1990. p. 2291–4.Google Scholar
  10. 10.
    Winston DJ. Prophylaxis and treatment of infection in the bone marrow transplant recipient. Curr Clin Top Infect Dis. 1993;13:293–321.PubMedGoogle Scholar
  11. 11.
    Meyers JD, Reed EC, Shepp DH, et al. Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic marrow transplantation. N Engl J Med. 1988;318:70–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Goodrich JM, Mori M, Gleaves CA, et al. Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N Engl J Med. 1991;325:1601–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Schmidt GM, Horak DA, Niland JC, et al. A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants; the City of Hope-Stanford-Syntex CMV Study Group. N Engl J Med. 1991;324:1005–11.PubMedCrossRefGoogle Scholar
  14. 14.
    Goodrich JM, Bowden RA, Fisher L, et al. Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant. Ann Intern Med. 1993;118:173–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Winston DJ, Ho WG, Bartoni K, et al. Ganciclovir prophylaxis of cytomegalovirus infection and disease in allogeneic bone marrow transplant recipients: results of a placebo-controlled, double-blind trial. Ann Intern Med. 1993;118:179–84.PubMedCrossRefGoogle Scholar
  16. 16.
    Merigan TC, Renlund DG, Keay S, et al. A controlled trial of ganciclovir to prevent cytomegalovirus disease after heart transplantation. N Engl J Med. 1992;326:1182–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Crumpacker CS. Ganciclovir. N Engl J Med. 1996;335:721–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Li CR, Greenberg PD, Gilbert MJ, et al. Recovery of HLArestricted cytomegalovirus (CMV)-specific T cell responses after allogeneic bone marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis. Blood. 1994;83:1971–9.PubMedGoogle Scholar
  19. 19.
    van den Berg AP, van Son WJ, Haagsma EB, et al. Prediction of recurrent cytomegalovirus disease after treatment with ganciclovir in solid organ transplant recipients. Transplantation. 1993;55:847–51.PubMedCrossRefGoogle Scholar
  20. 20.
    Boeckh M, Leisenring W, Riddell SR, et al. Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood. 2002;101:407–14.PubMedCrossRefGoogle Scholar
  21. 21.
    Hakki M, Riddell SR, Storek J, et al. Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation. Blood. 2003;102(8):3060–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Boeckh M, Riddell SR. Immunologic predictors of late cytomegalovirus disease after solid organ transplantation—an elusive goal? J Infect Dis. 2007;195(5):615–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Chemaly RF, Ullmann AJ, Stoelben S, Richard MP, Bornhäuser M, Groth C, Einsele H, Silverman M, Mullane KM, Brown J, Nowak H, Kölling K, Stobernack HP, Lischka P, Zimmermann H, Rübsamen-Schaeff H, Champlin RE, Ehninger G, AIC246 Study Team. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med. 2014;370(19):1781–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in hematopoietic stem cell transplant recipients. Infect Dis Clin North Am. 2010;24(2):319–37.PubMedCrossRefGoogle Scholar
  25. 25.
    Boeckh M. Complications, diagnosis, management, and prevention of CMV infections: current and future. Hematology Am Soc Hematol Educ Program. 2011;2011:305–9.PubMedGoogle Scholar
  26. 26.
    Marty FM, Ljungman P, Papanicolaou GA, Winston DJ, Chemaly RF, Strasfeld L, Young JA, Rodriguez T, Maertens J, Schmitt M, Einsele H, Ferrant A, Lipton JH, Villano SA, Chen H, Boeckh M; Maribavir 1263–300 Clinical Study Group. Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial. Lancet Infect Dis. 2011;11(4):284–92. doi: 10.1016/S1473-3099(11)70024-X. Epub 2011 Mar 21. Erratum in: Lancet Infect Dis. 2011;11(5):343.
  27. 27.
    Marty FM, Winston DJ, Rowley SD, Vance E, Papanicolaou GA, Mullane KM, Brundage TM, Robertson AT, Godkin S, Momméja-Marin H, Boeckh M, CMX001-201 Clinical Study Group. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369(13):1227–36.PubMedCrossRefGoogle Scholar
  28. 28.
    Boeckh M, Geballe AP. Cytomegalovirus: pathogen, paradigm, and puzzle. J Clin Invest. 2011;121(5):1673–80.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Boeckh M, Murphy WJ, Peggs KS. Reprint of: Recent advances in cytomegalovirus: an update on pharmacologic and cellular therapies. Biol Blood Marrow Transplant. 2015;21(2 Suppl):S19–24.PubMedCrossRefGoogle Scholar
  30. 30.
    Boeckh M, Nichols WG, Chemaly RF, Papanicolaou GA, Wingard JR, Xie H, Syrjala KL, Flowers ME, Stevens-Ayers T, Jerome KR, Leisenring W. Valganciclovir for the prevention of complications of late cytomegalovirus infection after allogeneic hematopoietic cell transplantation: a randomized trial. Ann Intern Med. 2015;162(1):1–10.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Comoli P, Basso S, Zecca M, et al. Preemptive therapy of EBV related lymphoproliferative disease after pediatric haploidentical stem cell transplantation. Am J Transplant. 2007;7(6):1648–55.PubMedCrossRefGoogle Scholar
  32. 32.
    Beersma MF, Bijlmakers MJ, Ploegh HL. Human cytomegalovirus down-regulates HLA class I expression by reducing the stability of class I H chains. J Immunol. 1993;151:4455–64.PubMedGoogle Scholar
  33. 33.
    Rawle FC, Tollefson AE, Wold WS, et al. Mouse anti-adenovirus cytotoxic T lymphocytes. Inhibition of lysis by E3 gp19K but not E3 14.7K. J Immunol. 1989;143:2031–7.PubMedGoogle Scholar
  34. 34.
    York IA, Roop C, Andrews DW, et al. A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell. 1994;77:525–35.PubMedCrossRefGoogle Scholar
  35. 35.
    Warren AP, Ducroq DH, Lehner PJ, et al. Human cytomegalovirus-infected cells have unstable assembly of major histocompatibility complex class I complexes and are resistant to lysis by cytotoxic T lymphocytes. J Virol. 1994;68:2822–9.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Biron CA, Byron KS, Sullivan JL. Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med. 1989;320:1731–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Welsh RM, Brubaker JO, Vargas-Cortes M, et al. Natural killer (NK) cell response to virus infections in mice with severe combined immunodeficiency. The stimulation of NK cells and the NK cell-dependent control of virus infections occur independently of T and B cell function. J Exp Med. 1991;173:1053–63.PubMedCrossRefGoogle Scholar
  38. 38.
    Reyburn HT, Mandelboim O, Vales-Gomez M, et al. The class I MHC homologue of human cytomegalovirus inhibits attack by natural killer cells. Nature. 1997;386:514–7.PubMedCrossRefGoogle Scholar
  39. 39.
    Rosenberg SA, Lotze MT, Muul LM, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985;313:1485–92.PubMedCrossRefGoogle Scholar
  40. 40.
    Miller JS, Cooley S, Parham P, et al. Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT. Blood. 2007;109(11):5058–61.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Miller JS, Weisdorf DJ, Burns LJ, et al. Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone. Blood. 2007;110(7):2761–3.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Passweg JR, Tichelli A, Meyer-Monard S. Purified donor NK lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation. Leukemia. 2004;18(11):1835–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Sciammas R, Johnson RM, Sperling AI, et al. Unique antigen recognition by a herpesvirus-specific TCR-gamma delta cell. J Immunol. 1994;152:5392–7.PubMedGoogle Scholar
  44. 44.
    Doherty PC, Allan W, Eichelberger M, et al. Roles of alpha beta and gamma delta T cell subsets in viral immunity. Annu Rev Immunol. 1992;10:123–51.PubMedCrossRefGoogle Scholar
  45. 45.
    Wilhelm M, Kunzmann V, Eckstein S, et al. Gamma delta T cells for immune therapy of patients with lymphoid malignancies. Blood. 2003;102(1):200–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Scheper W, van Dorp S, Kersting S, Pietersma F, Lindemans C, Hol S, Heijhuurs S, Sebestyen Z, Gründer C, Marcu-Malina V, Marchant A, Donner C, Plachter B, Vermijlen D, van Baarle D, Kuball J. γδT cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia. Leukemia. 2013;27(6):1328–38.PubMedCrossRefGoogle Scholar
  47. 47.
    Halary F, Pitard V, Dlubek D, et al. Shared reactivity of Vδ2neg γδ T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells. J Exp Med. 2005;201(10):1567–78.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Ahmed R. Immunological memory against viruses. Semin Immunol. 1992;4:105–9.PubMedGoogle Scholar
  49. 49.
    Hou S, Hyland L, Ryan KW, et al. Virus-specific CD8+ T cell memory determined by clonal burst size. Nature. 1994;369:652–4.PubMedCrossRefGoogle Scholar
  50. 50.
    Mackenzie CD, Taylor PM, Askonas BA. Rapid recovery of lung histology correlates with clearance of influenza virus by specific CD8+ cytotoxic T cells. Immunology. 1989;67:375–81.PubMedPubMedCentralGoogle Scholar
  51. 51.
    Nash AA, Jayasuriya A, Phelan J, et al. Different roles for L3T4+ and Lyt 2 + T cell subsets in the control of an acute herpes simplex virus infection of the skin and nervous system. J Gen Virol. 1987;68:825–33.PubMedCrossRefGoogle Scholar
  52. 52.
    Moskophidis D, Cobbold SP, Waldmann H, et al. Mechanism of recovery from acute virus infection: treatment of lymphocytic choriomeningitis virus-infected mice with monoclonal antibodies reveals that Lyt-2 + T lymphocytes mediate clearance of virus and regulate the antiviral antibody response. J Virol. 1987;61:1867–74.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Heslop HE, Leen AM. T-cell therapy for viral infections. Hematology Am Soc Hematol Educ Program. 2013;2013:342–7.PubMedGoogle Scholar
  54. 54.
    Rooney C, Leen A. Moving successful virus-specific T-cell therapy for hematopoietic stem cell recipients to late phase clinical trials. Mol Ther Nucleic Acids. 2012;1, e55.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Reddehase MJ, Weiland F, Munch K, et al. Interstitial murine cytomegalovirus pneumonia after irradiation: characterization of cells that limit viral replication during established infection of the lungs. J Virol. 1985;55:264–73.PubMedPubMedCentralGoogle Scholar
  56. 56.
    Raulet DH. MHC class I-deficient mice. Adv Immunol. 1994;55:381–421.PubMedCrossRefGoogle Scholar
  57. 57.
    Eichelberger M, Allan W, Zijlstra M, et al. Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8+ T cells. J Exp Med. 1991;174:875–80.PubMedCrossRefGoogle Scholar
  58. 58.
    Bender BS, Croghan T, Zhang L, et al. Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J Exp Med. 1992;175:1143–5.PubMedCrossRefGoogle Scholar
  59. 59.
    Cardell S, Merkenschlager M, Bodmer H, et al. The immune system of mice lacking conventional MHC class I molecules. Adv Immunol. 1994;55:423–40.PubMedCrossRefGoogle Scholar
  60. 60.
    Long EO. Antigen processing for presentation to CD4+ T cells. New Biol. 1992;4:274–82.PubMedGoogle Scholar
  61. 61.
    Yewdell JW, Bennink JR. The binary logic of antigen processing and presentation to T cells. Cell. 1990;62:203–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Malnati MS, Marti M, LaVaute T, et al. Processing pathways for presentation of cytosolic antigen to MHC class II-restricted T cells. Nature. 1992;357:702–4.PubMedCrossRefGoogle Scholar
  63. 63.
    Mosmann TR, Cherwinski H, Bond MW, et al. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986;136:2348–57.PubMedGoogle Scholar
  64. 64.
    Schoenberger SP, Toes RE, van der Voort EI, et al. T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions. Nature. 1998;393:480–3.PubMedCrossRefGoogle Scholar
  65. 65.
    Maggi E, Del Prete G, Macchia D, et al. Profiles of lymphokine activities and helper function for IgE in human T cell clones. Eur J Immunol. 1988;18:1045–50.PubMedCrossRefGoogle Scholar
  66. 66.
    Maggi E, Parronchi P, Manetti R, et al. Reciprocal regulatory effects of IFN-g and IL-4 and the in vitro development of human Th1 and Th2 clones. J Immunol. 1992;148:2142–7.PubMedGoogle Scholar
  67. 67.
    Mills KH. Induction, function and regulation of IL-17-producing T cells. Eur J Immunol. 2008;38(10):2636–49. Review.PubMedCrossRefGoogle Scholar
  68. 68.
    Mosmann TR, Moore KW. The role of IL-10 in cross-regulation of TH1 and TH2 responses. Immunol Today. 1991;12:A49–53.PubMedCrossRefGoogle Scholar
  69. 69.
    Seder RA, Gazzinelli R, Sher A, et al. Interleukin 12 acts directly on CD4+ T cells to enhance priming for interferon gamma production and diminishes interleukin 4 inhibition of such priming. Proc Natl Acad Sci U S A. 1993;90:10188–92.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Farrar JJ, Benjamin WR, Hilfiker ML, et al. The biochemistry, biology, and role of interleukin 2 in the induction of cytotoxic T cell and antibody-forming B cell responses. Immunol Rev. 1982;63:129–66.PubMedCrossRefGoogle Scholar
  71. 71.
    Biron CA, Young HA, Kasaian MT. Interleukin 2-induced proliferation of murine natural killer cells in vivo. J Exp Med. 1990;171:173–88.PubMedCrossRefGoogle Scholar
  72. 72.
    D’Souza WN, Schluns KS, Masopust D, et al. Essential role for IL-2 in the regulation of antiviral extralymphoid CD8 T cell responses. J Immunol. 2002;11:5566–72.CrossRefGoogle Scholar
  73. 73.
    Matloubian M, Concepcion RJ, Ahmed R. CD4+ T cells are required to sustain CD8+ cytotoxic T cell responses during chronic viral infection. J Virol. 1994;68:8056–63.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Staeheli P. Interferon-induced proteins and the antiviral state. Adv Virus Res. 1990;38:147–200.PubMedCrossRefGoogle Scholar
  75. 75.
    Wong GH, Goeddel DV. Tumour necrosis factors alpha and beta inhibit virus replication and synergize with interferons. Nature. 1986;323:819–22.PubMedCrossRefGoogle Scholar
  76. 76.
    Paul WE. Interleukin-4: a prototypic immunoregulatory lymphokine. Blood. 1991;77:1859–70.PubMedGoogle Scholar
  77. 77.
    Lopez AF, Sanderson CJ, Gamble JR, et al. Recombinant human interleukin 5 is a selective activator of human eosinophil function. J Exp Med. 1988;167:219–24.PubMedCrossRefGoogle Scholar
  78. 78.
    Graham MB, Braciale VL, Braciale TJ. Influenza virus-specific CD4 + T helper type 2 lymphocytes do not promote recovery from experimental virus infection. J Exp Med. 1994;180:1273–82.PubMedCrossRefGoogle Scholar
  79. 79.
    Alwan WH, Kozlowska WJ, Openshaw PJ. Distinct types of lung disease caused by functional subsets of antiviral T cells. J Exp Med. 1994;179:81–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Korn T, Oukka M, Kuchroo V, et al. Th17 cells: effector T cells with inflammatory properties. Semin Immunol. 2007;19(6):362–71. Review.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Yoshida H, Yoshiyuki M. Regulation of immune responses by interleukin-27. Immunol Rev. 2008;226(1):234–47.PubMedCrossRefGoogle Scholar
  82. 82.
    Boniface K, Blom B, Liu YJ, et al. From interleukin-23 to T-helper 17 cells: human T-helper cell differentiation revisited. Immunol Rev. 2008;226(1):132–46.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Korn T, Bettelli E, Oukka M, et al. IL-17 and Th17 cells. Annu Rev Immunol. 2009;27:485–517.PubMedCrossRefGoogle Scholar
  84. 84.
    Hou W, Kang HS, Kim B. Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection. J Exp Med. 2009;206(2):313–28.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Billerbeck E, Thimme R. CD8 + regulatory T cells in persistent human viral infections. Hum Immunol. 2008;69(11):771–5. Review.PubMedCrossRefGoogle Scholar
  86. 86.
    Ebinuma H, Nakamoto N, Li Y, et al. Identification and in vitro expansion of functional antigen-specific CD25+ FoxP3+ regulatory T cells in hepatitis C virus infection. J Virol. 2008;82(10):5043–53.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Belkaid Y, Oldenhove G. Tuning microenvironments: induction of regulatory T cells by dendritic cells. Immunity. 2008;29(3):362–71. Review.PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Joosten SA, Ottenhoff TH. Human CD4 and CD8 regulatory T cells in infectious diseases and vaccination. Hum Immunol. 2008;69(11):760–70. Review.PubMedCrossRefGoogle Scholar
  89. 89.
    Yewdell JW, Bennink JR. Cell biology of antigen processing and presentation to major histocompatibility complex class I molecule restricted T lymphocytes. Adv Immunol. 1992;52:1–123.PubMedCrossRefGoogle Scholar
  90. 90.
    Driscoll J, Brown MG, Finley D, et al. MHC-linked LMP gene products specifically alter peptidase activities of the proteosome. Nature. 1993;365:262–4.PubMedCrossRefGoogle Scholar
  91. 91.
    Spies T, DeMars R. Restored expression of major histocompatibility class I molecules by gene transfer of a putative peptide transporter. Nature. 1991;351:323–4.PubMedCrossRefGoogle Scholar
  92. 92.
    Appay V, Dunbar PR, Callan M, et al. Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med. 2002;4:379–85.CrossRefGoogle Scholar
  93. 93.
    Topp MS, Riddell SR, Akatsuka Y, et al. Restoration of CD28 expression in CD28+ CD8+ memory effector T cells reconstitutes antigen-induced IL-2 production. J Exp Med. 2003;198(6):947–55.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Doherty PC. Cell-mediated cytotoxicity. Cell. 1993;75:607–12.PubMedCrossRefGoogle Scholar
  95. 95.
    Kagi D, Ledermann B, Burki K, et al. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin deficient mice. Nature. 1994;369:31–7.PubMedCrossRefGoogle Scholar
  96. 96.
    Suwansirikul S, Rao N, Dowling JN, et al. Primary and secondary cytomegalovirus infection. Arch Intern Med. 1977;137:1026–9.PubMedCrossRefGoogle Scholar
  97. 97.
    Betts RF, Freeman RB, Douglas Jr RG, et al. Clinical manifestations of renal allograft derived primary cytomegalovirus infection. Am J Dis Child. 1977;131:759–63.PubMedGoogle Scholar
  98. 98.
    Reddehase MJ, Mutter W, Munch K, et al. CD8-positive T lymphocytes specific for marine cytomegalovirus immediate-early antigens mediate protective immunity. J Virol. 1987;61:3102–8.PubMedPubMedCentralGoogle Scholar
  99. 99.
    Reddehase MJ, Mutter W, Koszinowski UH. In vivo application of immune reconstitution strategies for prevention and recombinant interleukin 2 in the immunotherapy of established cytomegalovirus infection. J Exp Med. 1987;165:650–6.PubMedCrossRefGoogle Scholar
  100. 100.
    Lucin P, Pavic I, Polic B, et al. Gamma interferon-dependent clearance of cytomegalovirus infection in salivary glands. J Virol. 1992;66:1977–84.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Quinnan Jr GV, Kirmani N, Rook AH, et al. Cytotoxic T cells in cytomegalovirus infection: HLA-restricted T lymphocyte and non-T lymphocyte cytotoxic responses correlate with recovery from cytomegalovirus infection in bone-marrow-transplant recipients. N Engl J Med. 1982;307:7–13.PubMedCrossRefGoogle Scholar
  102. 102.
    Reusser P, Riddell SR, Meyers JD, et al. Cytotoxic T lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. Blood. 1991;78:1373–80.PubMedGoogle Scholar
  103. 103.
    Krause H, Hebart H, Jahn G, et al. Screening for CMV-specific T cell proliferation to identify patients at risk of developing late onset CMV disease. Bone Marrow Transplant. 1997;19:1111–6.PubMedCrossRefGoogle Scholar
  104. 104.
    Sester M, Sester U, Gartner B, et al. Sustained high frequencies of specific CD4 T cells restricted to a single persistent virus. J Virol. 2002;76:3748–55.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Cwynarski K, Ainsworth J, Cobbold M, et al. Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation. Blood. 2001;97:1232–40.PubMedCrossRefGoogle Scholar
  106. 106.
    Aubert G, Hassan-Walker AF, Madrigal JA, et al. Cytomegalovirus-specific cellular immune responses and viremia in recipients of allogeneic stem cell transplants. J Infect Dis. 2001;184:955–63.PubMedCrossRefGoogle Scholar
  107. 107.
    Gratama JW, Boeckh M, Nakamura R, Cornelissen JJ, Brooimans RA, Zaia JA, Forman SJ, Gaal K, Bray KR, Gasior GH, Boyce CS, Sullivan LA, Southwick PC. Immune monitoring with iTAg MHC Tetramers for prediction of recurrent or persistent cytomegalovirus infection or disease in allogeneic hematopoietic stem cell transplant recipients: a prospective multicenter study. Blood. 2010;116(10):1655–62.PubMedCrossRefGoogle Scholar
  108. 108.
    Mocarski Jr ES. Cytomegalovirus biology and replication. In: Roizman B, Whitley RJ, Lopez C, editors. The human herpesviruses. New York: Raven; 1993. p. 173–93.Google Scholar
  109. 109.
    Riddell SR, Rabin M, Geballe AP, et al. Class I MHC-restricted cytotoxic T lymphocyte recognition of cells infected with human cytomegalovirus does not require endogenous viral gene expression. J Immunol. 1991;146:2795–804.PubMedGoogle Scholar
  110. 110.
    McLaughlin-Taylor E, Pande H, Forman S, et al. Identification of the major late human cytomegalovirus matrix protein pp 65 as a target antigen for CD8+ virus-specific cytotoxic T lymphocytes. J Med Virol. 1994;43:103–10.PubMedCrossRefGoogle Scholar
  111. 111.
    Wills MR, Carmichael AJ, Mynard K, et al. The human cytotoxic T-lymphocyte (CTL) response to cytomegalovirus is dominated by structural protein pp 65: frequency, specificity, and T cell receptor usage of pp65 specific CTL. J Virol. 1996;70:7569–79.PubMedPubMedCentralGoogle Scholar
  112. 112.
    Boppana SB, Britt WJ. Recognition of human cytomegalovirus gene products by HCMV specific cytotoxic T cells. Virology. 1996;222:293–6.PubMedCrossRefGoogle Scholar
  113. 113.
    Borysiewicz LK, Hickling JK, Graham S, et al. Human cytomegalovirus-specific cytotoxic T cells. Relative frequency of stage-specific CTL recognizing the 72-kD immediate early protein and glycoprotein B expressed by recombinant vaccinia viruses. J Exp Med. 1988;168:919–31.PubMedCrossRefGoogle Scholar
  114. 114.
    Manley TJ, Luy L, Jones T, et al. Immune evasion proteins of human cytomegalovirus do not prevent a diverse CD8 + cytotoxic T-cell response in natural infection. Blood. 2004;104(4):1075–82.PubMedCrossRefGoogle Scholar
  115. 115.
    Khan N, Bruton R, Taylor GS, et al. Identification of cytomegalovirus-specific cytotoxic T lymphocytes in vitro is greatly enhanced by the use of recombinant virus lacking the US2 to US11 region or modified vaccinia virus Ankara expressing individual viral genes. J Virol. 2005;79(5):2869–79.PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Sylwester AW, Mitchell BL, Edgar JB, et al. Broadly targeted human cytomegalovirus-specific CD4 + and CD8 + T cells dominate the memory compartments of exposed subjects. J Exp Med. 2005;202(5):673–85.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    He H, Rinaldo Jr CR, Morel PA. T cell proliferative responses to five human cytomegalovirus proteins in healthy seropositive individuals: implications for vaccine development. J Gen Virol. 1995;76:1603–10.PubMedCrossRefGoogle Scholar
  118. 118.
    van Zanten J, Harmsen MC, van der Meer P, et al. Proliferative T cell responses to four human cytomegalovirus-specific proteins in healthy subjects and solid organ transplant recipients. J Infect Dis. 1995;172:879–82.PubMedCrossRefGoogle Scholar
  119. 119.
    Davignon JL, Clement D, Alriquet J, et al. Analysis of the proliferative T cell response to human cytomegalovirus major immediate early protein (IE1): phenotype, frequency and variability. Scand J Immunol. 1995;41:247–55.PubMedCrossRefGoogle Scholar
  120. 120.
    Liu YN, Klaus A, Kari B, et al. The N-terminal 513 amino acids of the envelope glycoprotein gB of human cytomegalovirus stimulates both B- and T-cell immune responses in humans. J Virol. 1991;65:1644–8.PubMedPubMedCentralGoogle Scholar
  121. 121.
    Kondo K, Xu J, Mocarski ES. Human cytomegalovirus latent gene expression in granulocyte-macrophage progenitors in culture and in seropositive individuals. Proc Natl Acad Sci U S A. 1996;93:11137–42.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Jones TR, Hanson LK, Sun L, et al. Multiple independent loci within the human cytomegalovirus unique short region downregulate expression of major histocompatibility complex class I heavy chains. J Virol. 1995;69:4830–41.PubMedPubMedCentralGoogle Scholar
  123. 123.
    Wiertz EJ, Jones TR, Sun L, et al. The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Cell. 1996;84:769–79.PubMedCrossRefGoogle Scholar
  124. 124.
    Jones TR, Wienz EJ, Sun L, et al. Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains. Proc Natl Acad Sci U S A. 1996;93:11327–33.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Wiertz EJ, Tortorella D, Bogyo M, et al. Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction. Nature. 1996;384:432–8.PubMedCrossRefGoogle Scholar
  126. 126.
    Hengel H, Koopmann JO, Flohr T, et al. A viral ER-resident glycoprotein inactivates the MHC-encoded peptide transporter. Immunity. 1997;6:623–32.PubMedCrossRefGoogle Scholar
  127. 127.
    Gilbert MJ, Riddell SR, Plachter B, et al. Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product. Nature. 1996;383:720–2.PubMedCrossRefGoogle Scholar
  128. 128.
    Tortorella D, Gewurz BE, Furman MH, et al. Viral subversion of the immune system [Review]. Annu Rev Immunol. 2000;18:861–926.PubMedCrossRefGoogle Scholar
  129. 129.
    Diefenbach A, Raulet DH. Strategies for target cell recognition by natural killer cells. Immunol Rev. 2001;181:170–84.PubMedCrossRefGoogle Scholar
  130. 130.
    Biassoni R, Cantoni C, Pende D, et al. Human natural killer cell receptors and co-receptors. Immunol Rev. 2001;181:203–14.PubMedCrossRefGoogle Scholar
  131. 131.
    Cosman D, Mullberg J, Sutherland CL, et al. ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity. 2001;14:123–33.PubMedCrossRefGoogle Scholar
  132. 132.
    Bauer S, Groh V, Wu J, et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science. 1999;285:727–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Diefenbach A, Jamieson AM, Liu SD, et al. Ligands for the murine NKG2D receptor: expression by tumor cells and activation of NK cells and macrophages. Nat Immunol. 2000;1:119–26.PubMedCrossRefGoogle Scholar
  134. 134.
    Cerwenka A, Bakker AB, McClanahan T, et al. Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice. Immunity. 2000;12:721–7.PubMedCrossRefGoogle Scholar
  135. 135.
    Malarkannan S, Shih PP, Eden PA, et al. The molecular and functional characterization of a dominant minor H antigen, H60. J Immunol. 1998;161:3501–9.PubMedGoogle Scholar
  136. 136.
    Groh V, Bahram S, Bauer S, et al. Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sci U S A. 1996;93:12445–50.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Groh V, Rhinehart R, Randolph-Habecker J, et al. Costimulation of CD8ab T cells by NKG2D via engagement by MIC induced on virus-infected cells. Nat Immunol. 2001;2:255–6.PubMedCrossRefGoogle Scholar
  138. 138.
    Welte SA, Sinzger C, Lutz SZ, et al. Selective intracellular retention of virally induced NKG2D ligands by human cytomegalovirus UL16 glycoprotein. Eur J Immunol. 2003;33:194–203.PubMedCrossRefGoogle Scholar
  139. 139.
    Haque T, Wilkie GM, Jones MM, et al. Allogeneic cytotoxic Tcell therapy for EBV-positive posttransplantation lymphoproliferative disease: results of a phase 2 multicenter clinical trial. Blood. 2007;110(4):1123–31.PubMedCrossRefGoogle Scholar
  140. 140.
    Schöttker B, Feuchtinger T, Schumm M, et al. Five donors-one recipient: modeling a mosaic of granulocytes, natural killer and T cells from cord-blood and third-party donors. Nat Clin Pract Oncol. 2008;5(5):291–5.PubMedCrossRefGoogle Scholar
  141. 141.
    Grigoleit GU, Kapp M, Hebart H, et al. Dendritic cell vaccination in allogeneic stem cell recipients: induction of human cytomegalovirus (HCMV)-specific cytotoxic T lymphocyte responses even in patients receiving a transplant from an HCMV-seronegative donor. J Infect Dis. 2007;196(5):699–704.PubMedCrossRefGoogle Scholar
  142. 142.
    Papadopoulos EB, Ladanyi M, Emanuel D, et al. Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation [see Comments]. N Engl J Med. 1994;330:1185–91.PubMedCrossRefGoogle Scholar
  143. 143.
    Einsele H, Roosnek E, Rufer N, Sinzger C, Riegler S, Löffler J, Grigoleit U, Moris A, Rammensee HG, Kanz L, Kleihauer A, Frank F, Jahn G, Hebart H. Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood. 2002;99(11):3916–22.Google Scholar
  144. 144.
    Walter EA, Greenberg PD, Gilbert MJ, et al. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T cell clones from the donor. N Engl J Med. 1995;333:1038–44.PubMedCrossRefGoogle Scholar
  145. 145.
    Rauser G, Einsele H, Sinzger C, et al. Rapid generation of combined CMV-specific CD4+ and CD8+ T-cell lines for adoptive transfer into recipients of allogeneic stem cell transplants. Blood. 2004;103(9):3565–72.PubMedCrossRefGoogle Scholar
  146. 146.
    Feuchtinger T, Opherk K, Bethge WA, Topp MS, Schuster FR, Weissinger EM, Mohty M, Or R, Maschan M, Schumm M, Hamprecht K, Handgretinger R, Lang P, Einsele H. Adoptive transfer of pp 65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. Blood. 2010;116(20):4360–7.PubMedCrossRefGoogle Scholar
  147. 147.
    Schmitt A, Tonn T, Busch DH, Grigoleit GU, Einsele H, Odendahl M, Germeroth L, Ringhoffer M, Ringhoffer S, Wiesneth M, Greiner J, Michel D, Mertens T, Rojewski M, Marx M, von Harsdorf S, Döhner H, Seifried E, Bunjes D, Schmitt M. Adoptive transfer and selective reconstitution of streptamer-selected cytomegalovirus-specific CD8+ T cells leads to virus clearance in patients after allogeneic peripheral blood stem cell transplantation. Transfusion. 2011;51(3):591–9.PubMedCrossRefGoogle Scholar
  148. 148.
    Odendahl M, Grigoleit GU, Bönig H, Neuenhahn M, Albrecht J, Anderl F, Germeroth L, Schmitz M, Bornhäuser M, Einsele H, Seifried E, Busch DH, Tonn T. Clinical-scale isolation of ‘minimally manipulated’ cytomegalovirus-specific donor lymphocytes for the treatment of refractory cytomegalovirus disease. Cytotherapy. 2014;16(9):1245–56.PubMedCrossRefGoogle Scholar
  149. 149.
    Stemberger C, Graef P, Odendahl M, Albrecht J, Dössinger G, Anderl F, Buchholz VR, Gasteiger G, Schiemann M, Grigoleit GU, Schuster FR, Borkhardt A, Versluys B, Tonn T, Seifried E, Einsele H, Germeroth L, Busch DH, Neuenhahn M. Lowest numbers of primary CD8(+) T cells can reconstitute protective immunity upon adoptive immunotherapy. Blood. 2014;124(4):628–37.PubMedCrossRefGoogle Scholar
  150. 150.
    Straus SE, Cohen JI, Tosato G, et al. NIH conference. Epstein-Barr virus infections: biology, pathogenesis, and management. Ann Intern Med. 1993;118:45–58.PubMedCrossRefGoogle Scholar
  151. 151.
    Moss DJ, Schmidt C, Elliott S, et al. Strategies involved in developing an effective vaccine for EBV-associated diseases. Adv Cancer Res. 1996;69:213–45.PubMedCrossRefGoogle Scholar
  152. 152.
    Levitskaya J, Coram M, Levitsky V, et al. Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1. Nature. 1995;375:685–8.PubMedCrossRefGoogle Scholar
  153. 153.
    Rickinson AB, Kieff E. Epstein-Barr virus. In: Fields BN, Knipe DM, Howley PM, editors. Fields virology. Philadelphia: Lippincott–Raven Publishers; 1996. p. 2397–446.Google Scholar
  154. 154.
    Cohen JI. Epstein-Barr virus lymphoproliferative disease associated with acquired immunodeficiency. Medicine. 1991;70:137–60.PubMedCrossRefGoogle Scholar
  155. 155.
    Zutter MM, Martin PJ, Sale GE, et al. Epstein-Barr virus lymphoproliferation after bone marrow transplantation. Blood. 1988;72:520–9.PubMedGoogle Scholar
  156. 156.
    Shapiro RS, McClain K, Frizzera G, et al. Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation. Blood. 1988;71:1234–43.PubMedGoogle Scholar
  157. 157.
    Caldas C, Ambinder R. Epstein-Barr virus and bone marrow transplantation. Curr Opin Oncol. 1995;7:102–6.PubMedCrossRefGoogle Scholar
  158. 158.
    Basgoz N, Preiksaitis JK. Post-transplant lymphoproliferative disorder. Infect Dis Clin North Am. 1995;9:901–23.PubMedGoogle Scholar
  159. 159.
    Young L, Alfieri C, Hennessy K, et al. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease. N Engl J Med. 1989;321:1080–5.PubMedCrossRefGoogle Scholar
  160. 160.
    Popescu I, Macedo C, Abu-Elmagd K, et al. EBV-specific CD8+ T cell reactivation in transplant patients results in expansion of CD8+ type-1 regulatory T cells. Am J Transplant. 2007;7(5):1215–23.PubMedCrossRefGoogle Scholar
  161. 161.
    Styczynski J, Reusser P, Einsele H, et al. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transplant. 2009;43:757–70.PubMedCrossRefGoogle Scholar
  162. 162.
    Martin PJ, Shulman HM, Schubach WH, et al. Fatal Epstein-Barr virus-associated proliferation of donor B cells alter treatment of acute graft-versus-host disease with a murine anti-T cell antibody. Ann Intern Med. 1984;101:310–5.PubMedCrossRefGoogle Scholar
  163. 163.
    Antin JH, Bierer BE, Smith BR, et al. Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies. Blood. 1991;78:2139–49.PubMedGoogle Scholar
  164. 164.
    Opelz G, Henderson R. Incidence of non-Hodgkin’s lymphoma in kidney and heart transplant recipients. Lancet. 1993;342:1514–6.PubMedCrossRefGoogle Scholar
  165. 165.
    Renard TH, Andrews WS, Foster ME. Relationship between OKT3 administration, EBV seroconversion, and the lymphoproliferative syndrome in pediatric liver transplant recipients. Transplant Proc. 1991;23:1473–6.PubMedGoogle Scholar
  166. 166.
    Swinnen LJ, Costanzo-Nordin MR, Fisher SG, et al. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients. N Engl J Med. 1990;323:1723–8.PubMedCrossRefGoogle Scholar
  167. 167.
    Rasche L, Kapp M, Einsele H, Mielke S. EBV-induced post transplant lymphoproliferative disorders: a persisting challenge in allogeneic hematopoetic SCT. Bone Marrow Transplant. 2014;49(2):163–7.PubMedCrossRefGoogle Scholar
  168. 168.
    Styczynski J, Einsele H, Gil L, Ljungman P. Outcome of treatment of Epstein-Barr virus-related post-transplant lymphoproliferative disorder in hematopoietic stem cell recipients: a comprehensive review of reported cases. Transpl Infect Dis. 2009;11(5):383–92.PubMedCrossRefGoogle Scholar
  169. 169.
    Walker RC, Paya CV, Marshall WF, et al. Pretransplantation seronegative Epstein-Barr virus status is the primary risk factor for posttransplantation lymphoproliferative disorder in adult heart, lung, and other solid organ transplantations. J Heart Lung Transplant. 1995;14:214–21.PubMedGoogle Scholar
  170. 170.
    van Esser JW, Niesters HG, Thijsen SF, et al. Molecular quantification of viral load in plasma allows for fast and accurate prediction of response to therapy of Epstein-Barr virus-associated lymphoproliferative disease after allogeneic stem cell transplantation. Br J Haematol. 2001;113:814–21.PubMedCrossRefGoogle Scholar
  171. 171.
    Styczynski J, Gil L, Tridello G, Ljungman P, Donnelly JP, van der Velden W, Omar H, Martino R, Halkes C, Faraci M, Theunissen K, Kalwak K, Hubacek P, Sica S, Nozzoli C, Fagioli F, Matthes S, Diaz MA, Migliavacca M, Balduzzi A, Tomaszewska A, Camara Rde L, van Biezen A, Hoek J, Iacobelli S, Einsele H, Cesaro S; Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Response to rituximab-based therapy and risk factor analysis in Epstein Barr Virus-related lymphoproliferative disorder after hematopoietic stem cell transplant in children and adults: a study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Clin Infect Dis. 2013;57(6):794–802.Google Scholar
  172. 172.
    Nolte A, Buhmann R, Straka C, et al. Assessment and characterization of the cytolytic T lymphocyte response against Epstein-Barr virus in patients with non-Hodgkin’s lymphoma after autologous peripheral blood stem cell transplantation. Bone Marrow Transplant. 1998;21:909–16.PubMedCrossRefGoogle Scholar
  173. 173.
    Lucas KG, Small TN, Heller G, et al. The development of cellular immunity to Epstein-Barr virus after allogeneic bone marrow transplantation. Blood. 1996;87:2594–603.PubMedGoogle Scholar
  174. 174.
    Rencher SD, Slobod KS, Smith FS, et al. Activity of transplanted CD8 + versus CD4 + cytotoxic T cells against Epstein-Barr virus immortalized B cell tumors in SCID mice. Transplantation. 1994;58:629–33.PubMedCrossRefGoogle Scholar
  175. 175.
    Buchsbaum RJ, Fabry JA, Lieberman J. EBV specific cytotoxic T lymphocytes protect against human EBV-associated lymphoma in SCID mice. Immunol Lett. 1996;52:145–52.PubMedCrossRefGoogle Scholar
  176. 176.
    O’Reilly RJ, Small TN, Papadopoulos E, et al. Biology and adoptive cell therapy of Epstein-Barr virus-associated lymphoproliferative disorders in recipients of marrow allografts. Immunol Rev. 1997;157:195–216.PubMedCrossRefGoogle Scholar
  177. 177.
    Lacerda JF, Ladanyi M, Louie DC, et al. Human Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes home preferentially to and induce selective regressions of autologous EBV induced B cell lymphoproliferations in xenografted C.B-17 scid/scid mice. J Exp Med. 1996;183:1215–28.Google Scholar
  178. 178.
    Murray RJ, Kurilla MG, Brooks JM, et al. Identification of target antigens for the human cytotoxic T cell response to Epstein-Barr virus (EBV): implications for the immune control of EBV positive malignancies. J Exp Med. 1992;176:157–68.PubMedCrossRefGoogle Scholar
  179. 179.
    Khanna R, Burrows SR, Kurilla MG, et al. Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development. J Exp Med. 1992;176:169–76.PubMedCrossRefGoogle Scholar
  180. 180.
    Paludan C, Bickham K, Nikiforow S, et al. Epstein-Barr nuclear antigen 1-specific CD4+ Th1 cells kill Burkitt’s lymphoma cells. J Immunol. 2002;169:1593–603.PubMedCrossRefGoogle Scholar
  181. 181.
    Rooney CM, Smith CA, Ng CY, et al. Use of gene-modified virus specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet. 1995;345:9–13.PubMedCrossRefGoogle Scholar
  182. 182.
    Heslop HE, Ng CY, Li C, et al. Long-term restoration of immunity against Epstein-Barr virus infection by adoptive transfer of gene-modified virus-specific T lymphocytes. Nat Med. 1996;2:551–5.PubMedCrossRefGoogle Scholar
  183. 183.
    Hammer MH, Brestrich G, Mittenzweig A, et al. Generation of EBV-specific T cells for adoptive immunotherapy: a novel protocol using formalin-fixed stimulator cells to increase biosafety. J Immunother. 2007;30(8):817–24.PubMedCrossRefGoogle Scholar
  184. 184.
    Gustafsson A, Levitsky V, Zou JZ, et al. Epstein-Barr virus (EBV) load in bone marrow transplant recipients at risk to develop posttransplant lymphoproliferative disease: prophylactic infusion of EBV-specific cytotoxic T cells. Blood. 2000;95:807–14.PubMedGoogle Scholar
  185. 185.
    Savoldo B, Huls MH, Liu Z, et al. Autologous Epstein-Barr Virus (EBV)-specific cytotoxic T cells for the treatment of persistent active EBV infection. Blood. 2002;100:4059–66.PubMedCrossRefGoogle Scholar
  186. 186.
    Gottschalk S, Ng CY, Perez M, et al. An Epstein-Barr virus deletion mutant associated with fatal lymphoproliferative disease unresponsive to therapy with virus-specific CTLs. Blood. 2001;97:835–43.PubMedCrossRefGoogle Scholar
  187. 187.
    Doubrovina E, Oflaz-Sozmen B, Prockop SE, Kernan NA, Abramson S, Teruya-Feldstein J, Hedvat C, Chou JF, Heller G, Barker JN, Boulad F, Castro-Malaspina H, George D, Jakubowski A, Koehne G, Papadopoulos EB, Scaradavou A, Small TN, Khalaf R, Young JW, O'Reilly RJ. Adoptive immunotherapy with unselected or EBV-specific T cells for biopsy-proven EBV+ lymphomas after allogeneic hematopoietic cell transplantation. Blood. 2012;119(11):2644–56.PubMedPubMedCentralCrossRefGoogle Scholar
  188. 188.
    Heslop HE, Slobod KS, Pule MA, Hale GA, Rousseau A, Smith CA, Bollard CM, Liu H, Wu MF, Rochester RJ, Amrolia PJ, Hurwitz JL, Brenner MK, Rooney CM. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood. 2010;115(5):925–35.PubMedPubMedCentralCrossRefGoogle Scholar
  189. 189.
    Wehler TC, Nonn M, Herr W, et al. Targeting the activation induced antigen CD137 can selectively deplete alloreactive T cells from antileukemic and antitumor donor T-cell lines. Blood. 2007;109(1):365–73.PubMedCrossRefGoogle Scholar
  190. 190.
    Wehler TC, Karg M, Herr W, et al. Rapid identification and sorting of viable virus-reactive CD4(+) and CD8(+) T cells based on antigen-triggered CD137 expression. J Immunol Methods. 2008;339(1):23–37.PubMedCrossRefGoogle Scholar
  191. 191.
    Khanna N, Stuehler C, Conrad B, Lurati S, Krappmann S, Einsele H, Berges C, Topp MS. Generation of a multipathogen-specific T-cell product for adoptive immunotherapy based on activation-dependent expression of CD154. Blood. 2011;118(4):1121–31.PubMedCrossRefGoogle Scholar
  192. 192.
    Dang Y, Knutson KL, Goodell V, et al. Tumor antigen-specific Tcell expansion is greatly facilitated by in vivo priming. Clin Cancer Res. 2007;13(6):1883–91.PubMedCrossRefGoogle Scholar
  193. 193.
    Feuchtinger T, Lang P, Hamprecht K, et al. Isolation and expansion of human adenovirus-specific CD4+ and CD8+ T cells according to IFN-gamma secretion for adjuvant immunotherapy. Exp Hematol. 2004;32(3):282–9.PubMedCrossRefGoogle Scholar
  194. 194.
    Feuchtinger T, Richard C, Joachim S, et al. Clinical grade generation of hexon-specific T cells for adoptive T-cell transfer as a treatment of adenovirus infection after allogeneic stem cell transplantation. J Immunother. 2008;31(2):199–206.PubMedCrossRefGoogle Scholar
  195. 195.
    Leen AM, Christin A, Khalil M, et al. Identification of hexon specific CD4 and CD8 T-cell epitopes for vaccine and immunotherapy. J Virol. 2008;82(1):546–54.PubMedCrossRefGoogle Scholar
  196. 196.
    Onion D, Crompton LJ, Milligan DW, et al. The CD4 + T-cell response to adenovirus is focused against conserved residues within the hexon protein. J Gen Virol. 2007;88(pt 9):2417–25.PubMedCrossRefGoogle Scholar
  197. 197.
    Heemskerk B, van Vreeswijk T, Veltrop-Duits LA, et al. Adenovirus-specific CD4+ T cell clones recognizing endogenous antigen inhibit viral replication in vitro through cognate interaction. J Immunol. 2006;177(12):8851–9.PubMedCrossRefGoogle Scholar
  198. 198.
    Chatziandreou I, Gilmour KC, McNicol AM, et al. Capture and generation of adenovirus specific T cells for adoptive immunotherapy. Br J Haematol. 2007;136(1):117–26.PubMedCrossRefGoogle Scholar
  199. 199.
    Feucht J, Opherk K, Lang P, Kayser S, Hartl L, Bethge W, Matthes-Martin S, Bader P, Albert MH, Maecker-Kolhoff B, Greil J, Einsele H, Schlegel PG, Schuster FR, Kremens B, Rossig C, Gruhn B, Handgretinger R, Feuchtinger T. Adoptive T-cell therapy with hexon-specific Th1 cells as a treatment of refractory adenovirus infection after HSCT. Blood. 2015;125(12):1986–94.PubMedCrossRefGoogle Scholar
  200. 200.
    Grazziutti M, Przepiorka D, Rex JH, et al. Dendritic cell mediated stimulation of the in vitro lymphocyte response to Aspergillus. Bone Marrow Transplant. 2001;27:647–52.PubMedCrossRefGoogle Scholar
  201. 201.
    Bozza S, Gaziano R, Spreca A, et al. Dendritic cells transport conidia and hyphae of Aspergillus fumigatus from the airways to the draining lymph nodes and initiate disparate Th responses to the fungus. J Immunol. 2002;168:1362–71.PubMedCrossRefGoogle Scholar
  202. 202.
    Bacci A, Montagnoli C, Perruccio K, et al. Dendritic cells pulsed with fungal RNA induce protective immunity to Candida albicans in hematopoietic transplantation. J Immunol. 2002;168:2904–13.PubMedCrossRefGoogle Scholar
  203. 203.
    Mencacci A, Perruccio K, Bacci A, et al. Defective antifungal T-helper 1 (TH1) immunity in a murine model of allogeneic T-cell-depleted bone marrow transplantation and its restoration by treatment with TH2 cytokine antagonists. Blood. 2001;97:1483–90.PubMedCrossRefGoogle Scholar
  204. 204.
    Garcia-Diaz JB, Palau L, Pankey GA. Resolution of rhinocerebral zygomycosis associated with adjuvant administration of granulocyte-macrophage colony-stimulating factor. Clin Infect Dis. 2001;32:166–70.CrossRefGoogle Scholar
  205. 205.
    Beck O, Topp MS, Koehl U, et al. Generation of highly purified and functionally active human TH1 cells against Aspergillus fumigatus. Blood. 2006;107(6):2562–9.PubMedCrossRefGoogle Scholar
  206. 206.
    Stuehler C, Khanna N, Bozza S, Zelante T, Moretti S, Kruhm M, Lurati S, Conrad B, Worschech E, Stevanović S, Krappmann S, Einsele H, Latgé JP, Loeffler J, Romani L, Topp MS. Cross-protective TH1 immunity against Aspergillus fumigatus and Candida albicans. Blood. 2011;117(22):5881–91.PubMedCrossRefGoogle Scholar
  207. 207.
    Bouzani M, Ok M, McCormick A, Ebel F, Kurzai O, Morton CO, Einsele H, Loeffler J. Human NK cells display important antifungal activity against Aspergillus fumigatus, which is directly mediated by IFN-γ release. J Immunol. 2011;187(3):1369–76.PubMedCrossRefGoogle Scholar
  208. 208.
    Bouzani M, Einsele H, Loeffler J. Functional analysis is a paramount prerequisite for understanding the in vitro interaction of human natural killer cells with Aspergillus fumigatus. J Infect Dis. 2012;205(6):1025–6. author reply 1026–7.PubMedCrossRefGoogle Scholar
  209. 209.
    Perruccio K, Tosti A, Velardi A, et al. Transferring functional immune responses to pathogens after haploidentical hematopoietic transplantation. Blood. 2005;106(13):4397–406.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Hermann Einsele
    • 1
  • Götz-Ulrich Grigoleit
    • 1
  • Stephan Mielke
    • 1
  1. 1.Department of Internal Medicine IIUniversity Hospital WuerzburgWuerzburgGermany

Personalised recommendations