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Reconstitution of the immune system after hematopoietic stem cell transplantation in humans

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Abstract

Hematopoietic stem cell transplantation is associated with a severe immune deficiency. As a result, the patient is at high risk of infections. Innate immunity, including epithelial barriers, monocytes, granulocytes, and NK cells recovers within weeks after transplantation. By contrast, adaptive immunity recovers much slower. B- and T-cell counts normalize during the first months after transplantation, but in particular, T-cell immunity may remain impaired for years. During the last decade, much of the underlying mechanisms have been identified. These insights may provide new therapies to accelerate recovery.

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References

  1. Witherspoon RP, Lum LG, Storb R (1984) Immunologic reconstitution after human marrow grafting. Semin Hematol 21:2–10

    PubMed  CAS  Google Scholar 

  2. Lum LG, Munn NA, Schanfield MS, Storb R (1986) The detection of specific antibody formation to recall antigens after human bone marrow transplantation. Blood 67:582–587

    PubMed  CAS  Google Scholar 

  3. Reusser P, Riddell SR, Meyers JD, Greenberg PD (1991) Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. Blood 78:1373–1380

    PubMed  CAS  Google Scholar 

  4. Lucas KG, Small TN, Heller G, Dupont B, O’Reilly RJ (1996) The development of cellular immunity to Epstein-Barr virus after allogeneic bone marrow transplantation. Blood 87:2594–2603

    PubMed  CAS  Google Scholar 

  5. Morrison VA, Haake RJ, Weisdorf DJ (1994) Non-Candida fungal infections after bone marrow transplantation: risk factors and outcome. Am J Med 96:497–503 doi:10.1016/0002-9343(94)90088-4

    PubMed  CAS  Google Scholar 

  6. Ochs L, Shu XO, Miller J, Enright H, Wagner J, Filipovich A, Miller W, Weisdorf D (1995) Late infections after allogeneic bone marrow transplantation: comparison of incidence in related and unrelated donor transplant recipients. Blood 86:3979–3986

    PubMed  CAS  Google Scholar 

  7. Storek J, Gooley T, Witherspoon RP, Sullivan KM, Storb R (1997) Infectious morbidity in long-term survivors of allogeneic marrow transplantation is associated with low CD4 T cell counts. Am J Hematol 54:131–138 doi:10.1002/(SICI)1096-8652(199702)54:2<131::AID-AJH6>3.0.CO;2-Y

    PubMed  CAS  Google Scholar 

  8. Storek J, Dawson MA, Storer B, Stevens-Ayers T, Maloney DG, Marr KA, Witherspoon RP, Bensinger W, Flowers ME, Martin P, Storb R, Appelbaum FR, Boeckh M (2001) Immune reconstitution after allogeneic marrow transplantation compared with blood stem cell transplantation. Blood 97:3380–3389 doi:10.1182/blood.V97.11.3380

    PubMed  CAS  Google Scholar 

  9. Antin JH (2002) Clinical practice. Long-term care after hematopoietic-cell transplantation in adults. N Engl J Med 347:36–42 doi:10.1056/NEJMcp010518

    PubMed  Google Scholar 

  10. Antin JH, Ferrara JL (1992) Cytokine dysregulation and acute graft-versus-host disease. Blood 80:2964–2968

    PubMed  CAS  Google Scholar 

  11. Bolotin E, Annett G, Parkman R, Weinberg K (1999) Serum levels of IL-7 in bone marrow transplant recipients: relationship to clinical characteristics and lymphocyte count. Bone Marrow Transplant 23:783–788 doi:10.1038/sj.bmt.1701655

    PubMed  CAS  Google Scholar 

  12. Chklovskaia E, Nowbakht P, Nissen C, Gratwohl A, Bargetzi M, Wodnar-Filipowicz A (2004) Reconstitution of dendritic and natural killer cell subsets after allogeneic stem cell transplantation: effects of endogenous flt3 ligand. Blood 103:3860 doi:10.1182/blood-2003–04–1200

    PubMed  CAS  Google Scholar 

  13. Gorochov G, Debré P, Leblond V, Sadat-Sowti B, Sigaux F, Autran B (1994) Oligoclonal expansion of CD8 + CD57 + T cells with restricted T-cell receptor b chain variability after bone marrow transplantation. Blood 83:587–595

    PubMed  CAS  Google Scholar 

  14. Gaschet J, Denis C, Milpied M, Hallet M-M, Romagné F, Necker A, Vivien R, David-Ameline J, Davodeau F, Bonneville M, Vié H (1995) Alterations of T cell repertoire after bone marrow transplantation: characterization of over-represented subsets. Bone Marrow Transplant 16:427–435

    PubMed  CAS  Google Scholar 

  15. Roux E, Helg C, Chapuis B, Jeannet M, Roosnek E (1996) T-cell repertoire complexity after allogeneic bone marrow transplantation. Hum Immunol 48:135–138 doi:10.1016/0198-8859(96)00085-7

    PubMed  CAS  Google Scholar 

  16. Small TN, Keever CA, Weiner-Fedus S, Heller G, O'Reilly RJ, Flomenberg N (1990) B-cell differentiation following autologous, conventional, or T-cell depleted bone marrow transplantation: a recapitulation of normal B-cell ontogeny. Blood 76:1647–1656

    PubMed  CAS  Google Scholar 

  17. Leino L, Lilius EM, Nikoskelainen J, Pelliniemi TT, Rajamaki A (1991) The reappearance of 10 differentiation antigens on peripheral blood lymphocytes after allogeneic bone marrow transplantation. Bone Marrow Transplant 8:339–344

    PubMed  CAS  Google Scholar 

  18. Storek J, Ferrara S, Ku N, Giorgi JV, Champlin RE, Saxon A (1993) B cell reconstitution after human bone marrow transplantation: recapitulation of ontogeny? Bone Marrow Transplant 12:387–398

    PubMed  CAS  Google Scholar 

  19. Storek J, King L, Ferrara S, Marcelo D, Saxon A, Braun J (1994) Abundance of a restricted fetal B cell repertoire in marrow transplant recipients. Bone Marrow Transplant 14:783–790

    PubMed  CAS  Google Scholar 

  20. Suzuki I, Milner ECB, Glas AM, Hufnagle WO, Rao SP, Pfister L, Nottenburg C (1996) Immunoglobulin heavy chain variable region gene usage in bone marrow transplant recipients: lack of somatic mutation indicates a maturational arrest. Blood 87:1873–1880

    PubMed  CAS  Google Scholar 

  21. Glas AM, van Montfort EH, Storek J, Green EG, Drissen RP, Bechtold VJ, Reilly JZ, Dawson MA, Milner EC (2000) B-cell-autonomous somatic mutation deficit following bone marrow transplant. Blood 96:1064–1069

    PubMed  CAS  Google Scholar 

  22. Gerritsen EJA, Van Tol MJD, Van't Veer MB, Wels JMA, Khouw IMSL, Touw CR, Jol-van der Zijde CM, Hermans J, Rümke HC, Radl J, Vossen JM (1994) Clonal dysregulation of the antibody response to tetanus-toxoid after bone marrow transplantation. Blood 84:4374–4382

    PubMed  CAS  Google Scholar 

  23. Storek J, Witherspoon RP, Luthy D, Storb R (1995) Low IgG production by mononuclear cells from marrow transplant survivors and from normal neonates is due to a defect of B cells. Bone Marrow Transplant 15:679–684

    PubMed  CAS  Google Scholar 

  24. Mackall CL, Fleisher TA, Brown MR, Andrich MP, Chen CC, Feuerstein IM, Horowitz ME, Magrath IT, Shad AT, Steinberg SM, Wexler LH, Gress RE (1995) Age, thymopoiesis, and CD4 + T-lymphocyte regeneration after intensive chemotherapy. N Engl J Med 332:143–149 doi:10.1056/NEJM199501193320303

    PubMed  CAS  Google Scholar 

  25. Small TN, Papadopoulos EB, Boulad F, Black P, Castro-Malaspina H, Childs BH, Collins N, Gillio A, George D, Jakubowski A, Heller G, Fazzari M, Kernan N, MacKinnon S, Szabolcs P, Young JW, O'Reilly RJ (1999) Comparison of immune reconstitution after unrelated and related T-cell- depleted bone marrow transplantation: effect of patient age and donor leukocyte infusions. Blood 93:467–480

    PubMed  CAS  Google Scholar 

  26. Hakim FT, Gress RE (2002) Reconstitution of thymic function after stem cell transplantation in humans. Curr Opin Hematol 9:490–496 doi:10.1097/00062752-200211000-00004

    PubMed  Google Scholar 

  27. Chaushu G, Itzkovitz-Chaushu S, Yefenof E, Slavin S, Or R, Garfunkel AA (1995) A longitudinal follow-up of salivary secretion in bone marrow transplant patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 79:164–169 doi:10.1016/S1079-2104(05)80276-8

    PubMed  CAS  Google Scholar 

  28. Noel DR, Witherspoon RP, Storb R, Atkinson K, Doney K, Mickelson EM, Ochs HD, Warren RP, Weiden PL, Thomas ED (1978) Does graft-versus-host disease influence the tempo of immunologic recovery after allogeneic human marrow transplantation? An observation on 56 long-term survivors. Blood 51:1087–1105

    PubMed  CAS  Google Scholar 

  29. Mullighan CG, Heatley S, Doherty K, Szabo F, Grigg A, Hughes TP, Schwarer AP, Szer J, Tait BD, Bik To L, Bardy PG (2002) Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation. Blood 99:3524–3529 doi:10.1182/blood.V99.10.3524

    PubMed  CAS  Google Scholar 

  30. Cornelissen J (2004) Hematopoietic reconstitution after hematopoietic stem cell transplantation. In: Atkinson KA, Champlin R, Ritz J, Fibbe WE, Ljungman P, Brenner MK (eds) Clinical bone marrow and blood stem cell transplantation. Cambridge University Press, Cambridge, pp 160–19

    Google Scholar 

  31. Zimmerli W, Zarth A, Gratwohl A, Speck B (1991) Neutrophil function and pyogenic infections in BMT recipients. Blood 77:393–399

    PubMed  CAS  Google Scholar 

  32. Nakata K, Gotoh H, Watanabe J, Uetake T, Komuro I, Yuasa K, Watanabe S, Ieki R, Sakamaki H, Akiyama H, Kudoh S, Naitoh M, Satoh H, Shimada K (1999) Augmented proliferation of human alveolar macrophages after allogeneic bone marrow transplantation. Blood 93:667–673

    PubMed  CAS  Google Scholar 

  33. Auffermann-Gretzinger S, Lossos IS, Vayntrub TA, Leong W, Grumet FC, Blume KG, Stockerl-Goldstein KE, Levy R, Shizuru JA (2002) Rapid establishment of dendritic cell chimerism in allogeneic hematopoietic cell transplant recipients. Blood 99:1442–1448 doi:10.1182/blood.V99.4.1442

    PubMed  CAS  Google Scholar 

  34. Cayeux S, Meuer S, Pezzutto A, Korbling M, Haas R, Schulz R, Dorken B (1989) Allogeneic mixed lymphocyte reactions during a second round of ontogeny: normal accessory cells did not restore defective IL-2 synthesis in T cells but induced responsiveness to exogeneous IL-2. Blood 74:2278–2284

    PubMed  CAS  Google Scholar 

  35. Sahdev I, O'Reilly R, Black P, Heller G, Hoffmann M (1996) Interleukin-1 production following T cell depleted and unmodified marrow grafts. Pediatr Hematol Oncol 13:55–67 doi:10.3109/08880019609033372

    PubMed  CAS  Google Scholar 

  36. Tsoi MS, Storb R, Brkic S, Ramberg E, Thomas ED, Storb R (1984) Cellular interactions in marrow-grafted patients, II, Normal monocyte antigen-presenting and defective T cell proliferative function early after grafting and during chronic graft-versus-host disease. Transplantation 37:556–561 doi:10.1097/00007890-198406000-00006

    PubMed  CAS  Google Scholar 

  37. Shiobara S, Witherspoon RP, Lum LG, Storb R (1984) Immunoglobulin synthesis after HLA-identical marrow grafting. V. The role of peripheral blood monocytes in the regulation of in vitro immunoglobulin secretion stimulated by pokeweed mitogen. J Immunol 132:2850–2856

    PubMed  CAS  Google Scholar 

  38. Brkic S, Tsoi MS, Mori T, Lachman L, Gillis S, Thomas ED, Storb R (1985) Cellular interactions in marrow-grafted patients. III. Normal interleukin-1 and defective interleukin-2 production in short-term patients and in those with chronic GVHD. Transplantation 39:30–35 doi:10.1097/00007890-198501000-00001

    PubMed  CAS  Google Scholar 

  39. Collin MP, Hart DN, Jackson GH, Cook G, Cavet J, Mackinnon S, Middleton PG, Dickinson AM (2006) The fate of human Langerhans cells in hematopoietic stem cell transplantation. J Exp Med 203:27–33 doi:10.1084/jem.20051787

    PubMed  CAS  Google Scholar 

  40. Dilly SA, Sloane JP (1988) Cellular composition of the spleen after human allogeneic bone marrow transplantation. J Pathol 155:151–160 doi:10.1002/path.1711550212

    PubMed  CAS  Google Scholar 

  41. Dilly SA, Sloane JP, Psalti IS (1986) The cellular composition of human lymph nodes after allogenic bone marrow transplantation: an immunohistological study. J Pathol 150:213–221 doi:10.1002/path.1711500310

    PubMed  CAS  Google Scholar 

  42. Horny HP, Ruck M, Kaiserling E, Ehninger G (1990) Immunohistology of the human spleen after bone marrow transplantation for leukemia with special reference to the early post-transplantation period. Pathol Res Pract 186:775–783

    PubMed  CAS  Google Scholar 

  43. Fearnley DB, Whyte LF, Carnoutsos SA, Cook AH, Hart DN (1999) Monitoring human blood dendritic cell numbers in normal individuals and in stem cell transplantation. Blood 93:728–736

    PubMed  CAS  Google Scholar 

  44. Klangsinsirikul P, Carter GI, Byrne JL, Hale G, Russell NH (2002) Campath-1G causes rapid depletion of circulating host dendritic cells (DCs) before allogeneic transplantation but does not delay donor DC reconstitution. Blood 99:2586–2591 doi:10.1182/blood.V99.7.2586

    PubMed  CAS  Google Scholar 

  45. Wu L, Li CL, Shortman K (1996) Thymic dendritic cell precursors: relationship to the T lymphocyte lineage and phenotype of the dendritic cell progeny. J Exp Med 184:903–911 doi:10.1084/jem.184.3.903

    PubMed  CAS  Google Scholar 

  46. Sale GE, Alavaikko M, Schaefers KM, Mahan CT (1992) Abnormal CD4:CD8 rations and delayed germinal center reconstitution in lymph nodes of human graft recipients with graft-versus-host disease: an immunohistological study. Exp Hematol 20:1017–1021

    PubMed  CAS  Google Scholar 

  47. Storek J, Witherspoon RP, Maloney DG, Chauncey TR, Storb R (1997) Improved reconstitution of CD4 T cells and B cells but worsened reconstitution of serum IgG levels after allogeneic transplantation of blood stem cells instead of marrow. Blood 89:3891–3893

    PubMed  CAS  Google Scholar 

  48. Merad M, Hoffmann P, Ranheim E, Slaymaker S, Manz MG, Lira SA, Charo I, Cook DN, Weissman IL, Strober S, Engleman EG (2004) Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease. Nat Med 10:510–517 doi:10.1038/nm1038

    PubMed  CAS  Google Scholar 

  49. Hokland M, Jacobsen N, Ellegaard J, Hokland P (1988) Natural killer function following allogeneic bone marrow transplantation. Very early reemergence but strong dependence of cytomegalovirus infection. Transplantation 45:1080–1084 doi:10.1097/00007890-198806000-00016

    PubMed  CAS  Google Scholar 

  50. Jacobs R, Stoll M, Stratmann G, Leo R, Link H, Schmidt RE (1992) CD16− CD56+ natural killer cells after bone marrow transplantation. Blood 79:3239–3244

    PubMed  CAS  Google Scholar 

  51. Ottinger HD, Beelen DW, Scheulen B, Schaefer UW, Grosse-Wilde H (1996) Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow. Blood 88:2775–2779

    PubMed  CAS  Google Scholar 

  52. Vitale C, Pitto A, Benvenuto F, Ponte M, Bellomo R, Frassoni F, Mingari MC, Bacigalupo A, Moretta L (2000) Phenotypic and functional analysis of the HLA-class I-specific inhibitory receptors of natural killer cells isolated from peripheral blood of patients undergoing bone marrow transplantation from matched unrelated donors. Hematol J 1:136–144 doi:10.1038/sj.thj.6200018

    PubMed  CAS  Google Scholar 

  53. Biron CA, Byron KS, Sullivan JL (1989) Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med 320:1731–1735

    PubMed  CAS  Google Scholar 

  54. Kuijpers TW, Baars PA, Dantin C, van den Burg M, van Lier RA, Roosnek E (2008) Human NK cells can control CMV infection in the absence of T cells. Blood 112:914–915 doi:10.1182/blood-2008-05-157354

    PubMed  CAS  Google Scholar 

  55. Kook H, Goldman F, Padley D, Giller R, Rumelhart S, Holida M, Lee N, Peters C, Comito M, Huling D, Trigg M (1996) Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children: immunophenotypic analysis and factors affecting the speed of recovery. Blood 88:1089–1097

    PubMed  CAS  Google Scholar 

  56. Shilling HG, McQueen KL, Cheng NW, Shizuru JA, Negrin RS, Parham P (2003) Reconstitution of NK cell receptor repertoire following HLA-matched hematopoietic cell transplantation. Blood 101:3730–3740 doi:10.1182/blood-2002-08-2568

    PubMed  CAS  Google Scholar 

  57. Vitale C, Chiossone L, Morreale G, Lanino E, Cottalasso F, Moretti S, Dini G, Moretta L, Mingari MC (2004) Analysis of the activating receptors and cytolytic function of human natural killer cells undergoing in vivo differentiation after allogeneic bone marrow transplantation. Eur J Immunol 34:455–460 doi:10.1002/eji.200324668

    PubMed  CAS  Google Scholar 

  58. Boyiadzis M, Memon S, Carson J, Allen K, Szczepanski MJ, Vance BA, Dean R, Bishop MR, Gress RE, Hakim FT (2008) Up-regulation of NK cell activating receptors following allogeneic hematopoietic stem cell transplantation under a lymphodepleting reduced intensity regimen is associated with elevated IL-15 levels. Biol Blood Marrow Transplant 14:290–300 doi:10.1016/j.bbmt.2007.12.490

    PubMed  CAS  Google Scholar 

  59. Dulphy N, Haas P, Busson M, Belhadj S, Peffault de Latour R, Robin M, Carmagnat M, Loiseau P, Tamouza R, Scieux C, Rabian C, Di Santo JP, Charron D, Janin A, Socie G, Toubert A (2008) An unusual CD56(bright) CD16(low) NK cell subset dominates the early posttransplant period following HLA-matched hematopoietic stem cell transplantation. J Immunol 181:2227–2237

    PubMed  CAS  Google Scholar 

  60. Loza MJ, Perussia B (2004) The IL-12 signature: NK cell terminal CD56 + high stage and effector functions. J Immunol 172:88–96

    PubMed  CAS  Google Scholar 

  61. Ferlazzo G, Thomas D, Lin SL, Goodman K, Morandi B, Muller WA, Moretta A, Munz C (2004) The abundant NK cells in human secondary lymphoid tissues require activation to express killer cell Ig-like receptors and become cytolytic. J Immunol 172:1455–1462

    PubMed  CAS  Google Scholar 

  62. Ruggeri L, Capanni M, Casucci M, Volpi I, Tosti A, Perruccio K, Urbani E, Negrin RS, Martelli MF, Velardi A (1999) Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood 94:333–339

    PubMed  CAS  Google Scholar 

  63. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, Posati S, Rogaia D, Frassoni F, Aversa F, Martelli MF, Velardi A (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295:2097–2100 doi:10.1126/science.1068440

    PubMed  CAS  Google Scholar 

  64. Leung W, Iyengar R, Turner V, Lang P, Bader P, Conn P, Niethammer D, Handgretinger R (2004) Determinants of antileukemia effects of allogeneic NK cells. J Immunol 172:644–650

    PubMed  CAS  Google Scholar 

  65. Ruggeri L, Mancusi A, Capanni M, Urbani E, Carotti A, Aloisi T, Stern M, Pende D, Perruccio K, Burchielli E, Topini F, Bianchi E, Aversa F, Martelli MF, Velardi A (2007) Donor natural killer cell allorecognition of missing self in haploidentical hematopoietic transplantation for acute myeloid leukemia: challenging its predictive value. Blood 110:433–440 doi:10.1182/blood-2006-07-038687

    PubMed  CAS  Google Scholar 

  66. Passweg JR, Huard B, Tiercy JM, Roosnek E (2007) HLA and KIR polymorphisms affect NK-cell anti-tumor activity. Trends Immunol 28:437–441 doi:10.1016/j.it.2007.07.008

    PubMed  CAS  Google Scholar 

  67. Gratama JW, Naipal A, Oljans P, Zwaan FE, Verdonck LF, De Witte T, Vossen JM, Bolhuis RL, de Gast GC, Jansen J (1984) T lymphocyte repopulation and differentiation after bone marrow transplantation. Early shifts in the ratio between T4+ and T8+ T lymphocytes correlate with the occurrence of acute graft-versus-host disease. Blood 63:1416–1423

    PubMed  CAS  Google Scholar 

  68. Ault KA, Antin JH, Ginsburg D, Orkin SH, Rappeport JM, Keohan ML, Martin P, Smith BR (1985) Phenotype of recovering lymphoid cell populations after marrow transplantation. J Exp Med 161:1483–1502 doi:10.1084/jem.161.6.1483

    PubMed  CAS  Google Scholar 

  69. Soiffer RJ, Bosserman L, Murray C, Cochran K, Daley J, Ritz J (1990) Reconstitution of T-cell function after CD6-depleted allogeneic bone marrow transplantation. Blood 75:2076–2084

    PubMed  CAS  Google Scholar 

  70. Holl RA, Dooren LJ, Vossen JM, Roos MT, Schellekens PT (1981) Bone marrow transplantation in children with severe aplastic anemia: reconstitution of cellular immunity. Transplantation 32:418–423 doi:10.1097/00007890-198111000-00016

    PubMed  CAS  Google Scholar 

  71. Roosnek E, Brouwer MC, Vossen JM, Roos MT, Schellekens PT, Zeijlemaker WP, Aarden LA (1987) The role of interleukin-2 in proliferative responses in vitro of T cells from patients after bone marrow transplantation. Evidence that minor defects can lead to in vitro unresponsiveness. Transplantation 43:855–860

    PubMed  CAS  Google Scholar 

  72. Roux E, Dumont-Girard F, Starobinski M, Siegrist C-A, Helg C, Chapuis B, Roosnek E (2000) Recovery of immune reactivity after T cell depleted bone marrow transplantation depends on thymic activity. Blood 96:2299–2303

    PubMed  CAS  Google Scholar 

  73. Mackall CL, Fleisher TA, Brown MR, Magrath IT, Shad AT, Horowitz ME, Wexler LH, Adde MA, McClure LL, Gress RE (1994) Lymphocyte depletion during treatment with intensive chemotherapy for cancer. Blood 84:2221–2228

    PubMed  CAS  Google Scholar 

  74. Mackall CL, Granger L, Sheard MA, Cepeda R, Gress RE (1993) T-cell regeneration after bone marrow transplantation: Differential CD45 isoform expression on thymic-derived versus thymic-independent progeny. Blood 82:2585–2594

    PubMed  CAS  Google Scholar 

  75. Weinberg K, Annett G, Kashyap A, Lenarsky C, Forman SJ, Parkman R (1995) The effect on thymic function on immunocompetence following bone marrow transplantation. Biol Blood Marrow Transplant 1:18–23

    PubMed  CAS  Google Scholar 

  76. Roux E, Helg C, Dumont-Girard F, Chapuis B, Jeannet M, Roosnek E (1996) Analysis of T cell repopulation after allogeneic bone marrow transplantation: significant differences between recipients of T cell depleted and unmanipulated grafts. Blood 87:3984–3992

    PubMed  CAS  Google Scholar 

  77. Mackall CL, Hakim FT, Gress RE (1997) Restoration of T-cell homeostasis after T-cell depletion. Semin Immunol 9:339–346 doi:10.1006/smim.1997.0091

    PubMed  CAS  Google Scholar 

  78. Dumont-Girard F, Roux E, Van Lier RA, Hale G, Helg C, Chapuis B, Starobinski M, Roosnek E (1998) Reconstitution of the T cell compartment after bone marrow transplantation: restoration of the repertoire by thymic emigrants. Blood 92:4464–4471

    PubMed  CAS  Google Scholar 

  79. Roux E, Abdi K, Speiser D, Helg C, Chapuis B, Jeannet M, Roosnek E (1993) Characterization of mixed chimerism in patients with chronic myeloid leukemia transplanted with T-cell-depleted bone marrow: involvement of different hematologic lineages before and after relapse. Blood 81:243–248

    PubMed  CAS  Google Scholar 

  80. Thude H, Hundrieser J, Wonigeit K, Schwinzer R (1995) A point mutation in the human CD45 gene associated with defective splicing of exon A. Eur J Immunol 25:2101–2106 doi:10.1002/eji.1830250745

    PubMed  CAS  Google Scholar 

  81. Rufer N, Helg C, Chapuis B, Roosnek E (2001) Human memory T cells: lessons from stem cell transplantation. Trends Immunol 22:136–141 doi:10.1016/S1471-4906(00)01849-4

    PubMed  CAS  Google Scholar 

  82. Hakim FT, Memon SA, Cepeda R, Jones EC, Chow CK, Kasten-Sportes C, Odom J, Vance BA, Christensen BL, Mackall CL, Gress RE (2005) Age-dependent incidence, time course, and consequences of thymic renewal in adults. J Clin Invest 115:930–939

    PubMed  CAS  Google Scholar 

  83. Jameson SC (2002) Maintaining the norm: T-Cell homeostasis. Nat Rev Immunol 2:547–556

    PubMed  CAS  Google Scholar 

  84. Goldrath AW, Bevan MJ (1999) Low-affinity ligands for the TCR drive proliferation of mature CD8+ T cells in lymphopenic hosts. Immunity 11:183–190 doi:10.1016/S1074-7613(00)80093-X

    PubMed  CAS  Google Scholar 

  85. Mackall CL, Bare CV, Granger LA, Sharrow SO, Titus JA, Gress RE (1996) Thymic-independent T cell regeneration occurs via antigen-driven expansion of peripheral T cells resulting in a repertoire that is limited in diversity and prone to skewing. J Immunol 156:4609–4616

    PubMed  CAS  Google Scholar 

  86. Soiffer RJ, Gonin R, Murray C, Robertson MJ, Cochran K, Chartier S, Cameron C, Daley J, Levine H, Nadler LM, Ritz J (1993) Prediction of graft-versus-host disease by phenotypic analysis of early immune reconstitution after CD6-depleted allogeneic bone marrow transplantation. Blood 82:2216–2223

    PubMed  CAS  Google Scholar 

  87. Mutis T, Gillespie G, Schrama E, Falkenburg JH, Moss P, Goulmy E (1999) Tetrameric HLA class I-minor histocompatibility antigen peptide complexes demonstrate minor histocompatibility antigen-specific cytotoxic T lymphocytes in patients with graft-versus-host disease. Nat Med 5:839–842 doi:10.1038/10563

    PubMed  CAS  Google Scholar 

  88. Gratama JW, van Esser JW, Lamers CH, Tournay C, Lowenberg B, Bolhuis RL, Cornelissen JJ (2001) Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8(+) T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection. Blood 98:1358–1364 doi:10.1182/blood.V98.5.1358

    PubMed  CAS  Google Scholar 

  89. Cwynarski K, Ainsworth J, Cobbold M, Wagner S, Mahendra P, Apperley J, Goldman J, Craddock C, Moss PA (2001) Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation. Blood 97:1232–1240 doi:10.1182/blood.V97.5.1232

    PubMed  CAS  Google Scholar 

  90. Falco DA, Nepomuceno RR, Krams SM, Lee PP, Davis MM, Salvatierra O, Alexander SR, Esquivel CO, Cox KL, Frankel LR, Martinez OM (2002) Identification of Epstein–Barr virus-specific CD8+ T lymphocytes in the circulation of pediatric transplant recipients. Transplantation 74:501–510 doi:10.1097/00007890–200208270–00012

    PubMed  CAS  Google Scholar 

  91. Chalandon Y, Degermann S, Villard J, Arlettaz L, Kaiser L, Vischer S, Walter S, Heemskerk MH, van Lier RA, Helg C, Chapuis B, Roosnek E (2006) The pre-transplant CMV-specific T-cells protect recipients of T-cell depleted grafts against cytomegalovirus related complications. Blood 187:389–396 doi:10.1182/blood-2005-07-2746

    Google Scholar 

  92. Storek J, Zhao Z, Lin E, Berger T, McSweeney PA, Nash RA, Akatsuka Y, Metcalf MD, Lu H, Kalina T, Reindl M, Storb R, Hansen JA, Sullivan KM, Kraft GH, Furst DE, Maloney DG (2004) Recovery from and consequences of severe iatrogenic lymphopenia (induced to treat autoimmune diseases). Clin Immunol 113:285–298 doi:10.1016/j.clim.2004.07.006

    PubMed  CAS  Google Scholar 

  93. Rufer N, Brümmendorf TH, Chapuis B, Helg C, Lansdorp PM, Roosnek E (2001) Accelerated telomere shortening is limited to the first year following stem cell transplantation. Blood 97:575–577 doi:10.1182/blood.V97.2.575

    PubMed  CAS  Google Scholar 

  94. Roelofs H, De Pauw ES, Zwinderman AH, Opdam SM, Willemze R, Tanke HJ, Fibbe WE (2002) Homeostasis of telomere length rather than telomere shortening after allogeneic peripheral blood stem cell transplantation. Blood 101:358–362 doi:10.1182/blood-2002-06-1832

    PubMed  Google Scholar 

  95. Thomson BG, Robertson KA, Gowan D, Heilman D, Broxmeyer HE, Emanuel D, Kotylo P, Brahmi Z, Smith FO (2000) Analysis of engraftment, graft-versus-host disease, and immune recovery following unrelated donor cord blood transplantation. Blood 96:2703–2711

    PubMed  CAS  Google Scholar 

  96. Verdonck LF, de Gast GC (1984) Is cytomegalovirus infection a major cause of T cell alterations after (autologous) bone-marrow transplantation? Lancet 1:932–935 doi:10.1016/S0140-6736(84)92391-2

    PubMed  CAS  Google Scholar 

  97. Janossy G, Prentice HG, Grob JP, Ivory K, Tidman N, Grundy J, Favrot M, Brenner MK, Campana D, Blacklock HA et al (1986) T lymphocyte regeneration after transplantation of T cell depleted allogeneic bone marrow. Clin Exp Immunol 63:577–586

    PubMed  CAS  Google Scholar 

  98. Eyrich M, Croner T, Leiler C, Lang P, Bader P, Klingebiel T, Niethammer D, Schlegel PG (2002) Distinct contributions of CD4(+) and CD8(+) naive and memory T-cell subsets to overall T-cell-receptor repertoire complexity following transplantation of T-cell-depleted CD34-selected hematopoietic progenitor cells from unrelated donors. Blood 100:1915–1918 doi:10.1182/blood-2001-11-0005

    PubMed  CAS  Google Scholar 

  99. Weinberg K, Blazar BR, Wagner JE, Agura E, Hill BJ, Smogorzewska M, Koup RA, Betts MR, Collins RH, Douek DC (2001) Factors affecting thymic function after allogeneic hematopoietic stem cell transplantation. Blood 97:1458–1466 doi:10.1182/blood.V97.5.1458

    PubMed  CAS  Google Scholar 

  100. Singhal S, Mehta J (1999) Reimmunization after blood or marrow stem cell transplantation. Bone Marrow Transplant 23:637–646 doi:10.1038/sj.bmt.1701640

    PubMed  CAS  Google Scholar 

  101. Avigan D, Pirofski LA, Lazarus HM (2001) Vaccination against infectious disease following hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 7:171–183 doi:10.1053/bbmt.2001.v7.pm11302551

    PubMed  CAS  Google Scholar 

  102. Ljungman P, Engelhard D, de la Camara R, Einsele H, Locasciulli A, Martino R, Ribaud P, Ward K, Cordonnier C (2005) Vaccination of stem cell transplant recipients: recommendations of the infectious diseases working party of the EBMT. Bone Marrow Transplant 35:737–746 doi:10.1038/sj.bmt.1704870

    PubMed  CAS  Google Scholar 

  103. Montagna D, Locatelli F, Moretta A, Lisini D, Previdere C, Grignani P, DeStefano P, Giorgiani G, Montini E, Pagani S, Comoli P, Maccario R (2004) T lymphocytes of recipient origin may contribute to the recovery of specific immune response towards viruses and fungi in children given cord blood transplantation. Blood 103:4322–4329 doi:10.1182/blood-2003-11-4041

    PubMed  CAS  Google Scholar 

  104. Wimperis JZ, Brenner MK, Prentice HG, Reittie JE, Karayiannis P, Griffiths PD, Hoffbrand AV (1986) Transfer of a functioning humoral immune system in transplantation of T-lymphocyte-depleted bone marrow. Lancet 1:339–343 doi:10.1016/S0140-6736(86)92315-9

    PubMed  CAS  Google Scholar 

  105. Saxon A, Mitsuyasu R, Stevens R, Champlin RE, Kimata H, Gale RP (1986) Designed transfer of specific immune responses with bone marrow transplantation. J Clin Invest 78:959–967 doi:10.1172/JCI112686

    PubMed  CAS  Google Scholar 

  106. de Gast GC, Gratama JW, Verdonck LF, van Heugten JG, Zwaan FE, Phillips DI, Mudde GC (1989) The influence of T cell depletion on recovery of T cell proliferation to herpesviruses and Candida after allogeneic bone marrow transplantation. Transplantation 48:111–115 doi:10.1097/00007890-198907000-00026

    PubMed  Google Scholar 

  107. Wimperis JZ, Gottlieb D, Duncombe AS, Heslop HE, Prentice HG, Brenner MK (1990) Requirements for the adoptive transfer of antibody responses to a priming antigen in man. J Immunol 144:541–547

    PubMed  CAS  Google Scholar 

  108. Labadie J, van Tol MJ, Dijkstra NH, Zwaan FE, Vossen JM (1992) Transfer of specific immunity from donor to recipient of an allogeneic bone marrow graft: effect of conditioning on the specific immune response of the graft recipient. Br J Haematol 80:381–390 doi:10.1111/j.1365-2141.1992.tb08149.x

    PubMed  CAS  Google Scholar 

  109. Molrine DC, Guinan EC, Antin JH, Parsons SK, Weinstein HJ, Wheeler C, McGarigle C, Blanding P, Phillips NR, Kinsella K, Deans K, Ciamarra A, Goorin A, George S, Ambrosino DM (1996) Donor immunization with Haemophilus influenzae type b (HIB)-conjugate vaccine in allogeneic bone marrow transplantation. Blood 87:3012–3018

    PubMed  CAS  Google Scholar 

  110. Gerritsen EJA, Van Tol MJD, Lankester AC, Van der Weijden-Ragas CPM, Jol-van der Zijde CM, Oudeman-Gruber NJ, Radl J, Vossen JM (1993) Immunoglobulin levels and monoclonal gammopathies in children after bone marrow transplantation. Blood 82:3493–3502

    PubMed  CAS  Google Scholar 

  111. Parkman R, Weinberg KI (1997) Immunological reconstitution following bone marrow transplantation. Immunol Rev 157:73–78 doi:10.1111/j.1600-065X.1997.tb00975.x

    PubMed  CAS  Google Scholar 

  112. Ljungman P, Wiklund-Hammarsten M, Duraj V, Hammarstrom L, Lonnqvist B, Paulin T, Ringden O, Pepe MS, Gahrton G (1990) Response to tetanus toxoid immunization after allogeneic bone marrow transplantation. J Infect Dis 162:496–500

    PubMed  CAS  Google Scholar 

  113. Chakrabarti S, Milligan DW, Pillay D, Mackinnon S, Holder K, Kaur N, McDonald D, Fegan CD, Waldmann H, Hale G, Rickinson A, Steven N (2003) Reconstitution of the Epstein–Barr virus-specific cytotoxic T-lymphocyte response following T-cell-depleted myeloablative and nonmyeloablative allogeneic stem cell transplantation. Blood 102:839–842 doi:10.1182/blood.V102.3.839

    PubMed  CAS  Google Scholar 

  114. Storek J, Dawson MA, Lim LC, Burman BE, Stevens-Ayers T, Viganego F, Herremans MM, Flowers ME, Witherspoon RP, Maloney DG, Boeckh M (2004) Efficacy of donor vaccination before hematopoietic cell transplantation and recipient vaccination both before and early after transplantation. Bone Marrow Transplant 33:337–346 doi:10.1038/sj.bmt.1704336

    PubMed  CAS  Google Scholar 

  115. Chen CS, Boeckh M, Seidel K, Clark JG, Kansu E, Madtes DK, Wagner JL, Witherspoon RP, Anasetti C, Appelbaum FR, Bensinger WI, Deeg HJ, Martin PJ, Sanders JE, Storb R, Storek J, Wade J, Siadak M, Flowers ME, Sullivan KM (2003) Incidence, risk factors, and mortality from pneumonia developing late after hematopoietic stem cell transplantation. Bone Marrow Transplant 32:515–522 doi:10.1038/sj.bmt.1704162

    PubMed  Google Scholar 

  116. Grob JP, Grundy JE, Prentice HG, Griffiths PD, Hoffbrand AV, Hughes MD, Tate T, Wimperis JZ, Brenner MK (1987) Immune donors can protect marrow-transplant recipients from severe cytomegalovirus infections. Lancet 1:774–776 doi:10.1016/S0140-6736(87)92800-5

    PubMed  CAS  Google Scholar 

  117. Wimperis JZ, Berry NJ, Prentice HG, Lever A, Griffiths PD, Brenner MK (1987) Regeneration of humoral immunity to herpes simplex virus following T-cell-depleted allogeneic bone marrow transplantation. J Med Virol 23:93–99 doi:10.1002/jmv.1890230111

    PubMed  CAS  Google Scholar 

  118. Wimperis JZ, Brenner MK, Prentice HG, Thompson EJ, Hoffbrand AV (1987) B cell development and regulation after T cell-depleted marrow transplantation. J Immunol 138:2445–2450

    PubMed  CAS  Google Scholar 

  119. Schmeiser T, Wiesneth M, Bunjes D, Arnold R, Hertenstein B, Heit W, Kurrle E (1989) Infectious complications after allogeneic bone marrow transplantation with and without T-cell depletion of donor marrow. Infection 17:124–130 doi:10.1007/BF01644010

    PubMed  CAS  Google Scholar 

  120. Anderson KC, Soiffer R, DeLage R, Takvorian T, Freedman AS, Rabinowe SL, Nadler LM, Dear K, Heflin L, Mauch P et al (1990) T-cell-depleted autologous bone marrow transplantation therapy: analysis of immune deficiency and late complications. Blood 76:235–244

    PubMed  CAS  Google Scholar 

  121. Gandhi MK, Wills MR, Okecha G, Day EK, Hicks R, Marcus RE, Sissons JG, Carmichael AJ (2003) Late diversification in the clonal composition of Human Cytomegalovirus-specific CD8+ T-cells following allogeneic haemopoietic stem cell transplantation. Blood 102:3427–3438 doi:10.1182/blood-2002-12-3689

    PubMed  CAS  Google Scholar 

  122. Heitger A, Neu N, Kern H, Panzer-Grumayer ER, Greinix H, Nachbaur D, Niederwieser D, Fink FM (1997) Essential role of the thymus to reconstitute naive (CD45RA+) T-helper cells after human allogeneic bone marrow transplantation. Blood 90:850–857

    PubMed  CAS  Google Scholar 

  123. Storek J, Joseph A, Dawson MA, Douek DC, Storer B, Maloney DG (2002) Factors influencing T-lymphopoiesis after allogeneic hematopoietic cell transplantation. Transplantation 73:1154–1158 doi:10.1097/00007890-200204150-00026

    PubMed  Google Scholar 

  124. Haynes BF, Markert ML, Sempowski GD, Patel DD, Hale LP (2000) The role of the thymus in immune reconstitution in aging, bone marrow transplantation, and HIV-1 infection. Annu Rev Immunol 18:529–560

    PubMed  CAS  Google Scholar 

  125. Storek J, Witherspoon RP, Webb D, Storb R (1996) Lack of B cell precursors in marrow transplant recipients with chronic GVHD. Am J Hematol 52:82–89 doi:10.1002/(SICI)1096-8652(199606)52:2<82::AID-AJH3>3.0.CO;2-1

    PubMed  CAS  Google Scholar 

  126. Storek J, Wells D, Dawson MA, Storer B, Maloney DG (2001) Factors influencing B lymphopoiesis after allogeneic hematopoietic cell transplantation. Blood 98:489–491 doi:10.1182/blood.V98.2.489

    PubMed  CAS  Google Scholar 

  127. Sullivan KM, Storek J, Kopecky KJ, Jocom JJ, Longton G, Flowers M, Siadak M, Nims J, Witherspoon RP, Anasetti C, Bowden R, Applebaum FR, Buckner CD, Deeg HJ, Hansen JA, McDonald GB, Sanders JE, Storb R (1996) A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic GVHD following marrow transplantation: clinical outcome and effect on subsequent immune recovery. Biol Blood Marrow Transplant 2:44–53

    PubMed  CAS  Google Scholar 

  128. Ljungman P, Lewensohn-Fuchs I, Hammarström V, Aschan J, Brandt L, Bolme P, Lonnqvist B, Johansson N, Ringden O, Gahrton G (1994) Long-term immunity to measles, mumps, and rubella after allogeneic bone marrow transplantation. Blood 84:657–663

    PubMed  CAS  Google Scholar 

  129. Engelhard D, Weinberg M, Or R, Shaked O, Naparstek E, Haikin H, Slavin S, Sarov I (1991) Immunoglobulins A, G, and M to cytomegalovirus during recurrent infection in recipients of allogeneic bone marrow transplantation. J Infect Dis 163:628–630

    PubMed  CAS  Google Scholar 

  130. Lutz E, Ward KN, Szydlo R, Goldman JM (1996) Cytomegalovirus antibody avidity in allogeneic bone marrow recipients: evidence for primary or secondary humoral responses depending on donor immune status. J Med Virol 49:61–65 doi:10.1002/(SICI)1096-9071(199605)49:1<61::AID-JMV10>3.0.CO;2-5

    PubMed  CAS  Google Scholar 

  131. Lortan JE, Vellodi A, Jurges ES, Hugh-Jones K (1992) Class- and subclass-specific pneumococcal antibody levels and response to immunization after bone marrow transplantation. Clin Exp Immunol 88:512–519

    PubMed  CAS  Google Scholar 

  132. Storek J, Joseph A, Espino G, Dawson MA, Douek DC, Sullivan KM, Flowers ME, Martin P, Mathioudakis G, Nash RA, Storb R, Appelbaum FR, Maloney DG (2001) Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation. Blood 98:3505–3512 doi:10.1182/blood.V98.13.3505

    PubMed  CAS  Google Scholar 

  133. Storek J, Witherspoon RP (2004) Immunological reconstitution after hemopoietic stem cell transplantation. In: Atkinson K, Champlin R, Ritz J, Fibbe WE, Ljungman P, Brenner MK (eds) Clinical bone marrow and blood stem cell transplantation. Cambridge University Press, Cambridge, pp 194–226

    Google Scholar 

  134. Guinan EC, Molrine DC, Antin JH, Lee MC, Weinstein HJ, Sallan SE, Parsons SK, Wheeler C, Gross W, McGarigle C, Blanding P, Schiffman G, Finberg RW, Siber GR, Bolon D, Wang M, Cariati S, Ambrosino DM (1994) Polysaccharide conjugate vaccine responses in bone marrow transplant patients. Transplantation 57:677–684 doi:10.1097/00007890-199403150-00009

    PubMed  CAS  Google Scholar 

  135. Miller JJ, Cole LJ (1967) The radiation resistance of long-lived lymphocytes and plasma cells in mouse and rat lymph nodes. J Immunol 98:982–990

    PubMed  CAS  Google Scholar 

  136. Slifka MK, Antia R, Whitmire JK, Ahmed R (1998) Humoral immunity due to long-lived plasma cells. Immunity 8:363–372 doi:10.1016/S1074-7613(00)80541-5

    PubMed  CAS  Google Scholar 

  137. Asma GEM, Langois R, VanDenBergh RL, Vossen JM (1987) Regeneration of TdT+, pre-B and B cells in bone marrow after allogeneic bone marrow transplantation. Transplantation 43:865–870

    Article  PubMed  CAS  Google Scholar 

  138. Uckun FM, Haissig S, Ledbetter JA, Fidler P, Myers DE, Kuebelbeck V, Weisdorf D, Gajl-Peczalska K, Kersey JH, Ramsay KC (1992) Developmental hierarchy during early human B cell ontogeny after autologous bone marrow transplantation using autografts depleted of CD19 + B cell precursors by an anti-CD19 pan-B-cell immunotoxin containing pokeweed antiviral protein. Blood 79:3369–3379

    PubMed  CAS  Google Scholar 

  139. Leitenberg D, Rappeport JM, Smith BR (1994) B cell precursor bone marrow reconstitution after bone marrow transplantation. Am J Clin Pathol 102:231–236

    PubMed  CAS  Google Scholar 

  140. Baumgartner C, Morell A, Hirt A, Bucher U, Forster HK, Doran JE, Matter L, DelRe GB, Wagner HP (1988) Humoral immune function in pediatric patients treated with autologous bone marrow transplantation for B cell non-Hodgkin’s lymphoma: The influence of ex vivo marrow decontamination with anti-Y29/55 monoclonal antibody and complement. Blood 71:1211–1217

    PubMed  CAS  Google Scholar 

  141. Bengtsson M, Smedmyr B, Festin R, Oberg G, Simonsson B, Totterman TH (1989) B lymphocyte regeneration in marrow and blood after autologous bone marrow transplantation: increased numbers of B cells carrying activation and progression markers. Leuk Res 13:791–797 doi:10.1016/0145-2126(89)90092-1

    PubMed  CAS  Google Scholar 

  142. Pedrazzini A, Freedman AS, Andersen J, Heflin L, Anderson K, Takvorian T, Canellos GP, Whitman J, Coral F, Ritz J, Nadler LM (1989) Anti-B cell monoclonal antibody-purged autologous BMT for B cell non-Hodgkin’s lymphoma: Phenotypic reconstitution and B cell function. Blood 74:2203–2211

    PubMed  CAS  Google Scholar 

  143. Cutler C, Giri S, Jeyapalan S, Paniagua D, Viswanathan A, Antin JH (2001) Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem-cell and bone marrow transplantation: a meta-analysis. J Clin Oncol 19:3685–3691

    PubMed  CAS  Google Scholar 

  144. Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED, Riddell SR (1995) 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 333:1038–1044 doi:10.1056/NEJM199510193331603

    PubMed  CAS  Google Scholar 

  145. O’Reilly RJ, Lacerda JF, Lucas KG, Rosenfield NS, Small TN, Papadopoulos EB (1996) Adoptive cell therapy with donor lymphocytes for EBV-associated lymphomas developing after allogeneic marrow transplants. Important Adv Oncol 149–166

  146. Rooney CM, Smith CA, Ng CY, Loftin SK, Sixbey JW, Gan Y, Srivastava DK, Bowman LC, Krance RA, Brenner MK, Heslop HE (1998) Infusion of cytotoxic T cells for the prevention and treatment of Epstein–Barr virus-induced lymphoma in allogeneic transplant recipients. Blood 92:1549–1555

    PubMed  CAS  Google Scholar 

  147. Einsele H, Roosnek E, Rufer N, Sinzger C, Riegler S, Loffler J, Grigoleit U, Moris A, Rammensee HG, Kanz L, Kleihauer A, Frank F, Jahn G, Hebart H (2002) Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood 99:3916–3922 doi:10.1182/blood.V99.11.3916

    PubMed  CAS  Google Scholar 

  148. Peggs KS, Verfuerth S, Pizzey A, Khan N, Guiver M, Moss PA, Mackinnon S (2003) Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines. Lancet 362:1375–1377 doi:10.1016/S0140-6736(03)14634-X

    PubMed  Google Scholar 

  149. Cobbold M, Khan N, Pourgheysari B, Tauro S, McDonald D, Osman H, Assenmacher M, Billingham L, Steward C, Crawley C, Olavarria E, Goldman J, Chakraverty R, Mahendra P, Craddock C, Moss PA (2005) Adoptive transfer of cytomegalovirus-specific CTL to stem cell transplant patients after selection by HLA-peptide tetramers. J Exp Med 202:379–386 doi:10.1084/jem.20040613

    PubMed  CAS  Google Scholar 

  150. Feuchtinger T, Matthes-Martin S, Richard C, Lion T, Fuhrer M, Hamprecht K, Handgretinger R, Peters C, Schuster FR, Beck R, Schumm M, Lotfi R, Jahn G, Lang P (2006) Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation. Br J Haematol 134:64–76 doi:10.1111/j.1365-2141.2006.06108.x

    PubMed  Google Scholar 

  151. Leen AM, Myers GD, Sili U, Huls MH, Weiss H, Leung KS, Carrum G, Krance RA, Chang CC, Molldrem JJ, Gee AP, Brenner MK, Heslop HE, Rooney CM, Bollard CM (2006) Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat Med 12:1160–1166 doi:10.1038/nm1475

    PubMed  CAS  Google Scholar 

  152. Andre-Schmutz I, Le Deist F, Hacein-Bey-Abina S, Vitetta E, Schindler J, Chedeville G, Vilmer E, Fischer A, Cavazzana-Calvo M (2002) Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: a phase 1/2 study. Lancet 360:130–137 doi:10.1016/S0140-6736(02)09413-8

    PubMed  Google Scholar 

  153. Mielke S, Solomon SR, Barrett AJ (2005) Selective depletion strategies in allogeneic stem cell transplantation. Cytotherapy 7:109–115 doi:10.1080/14653240510018172

    PubMed  CAS  Google Scholar 

  154. Amrolia PJ, Muccioli-Casadei G, Huls H, Adams S, Durett A, Gee A, Yvon E, Weiss H, Cobbold M, Gaspar HB, Rooney C, Kuehnle I, Ghetie V, Schindler J, Krance R, Heslop HE, Veys P, Vitetta E, Brenner MK (2006) Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplant. Blood 108:1797–1808 doi:10.1182/blood-2006-02-001909

    PubMed  CAS  Google Scholar 

  155. Kalina T, Lu H, Zhao Z, Blewett E, Dittmer DP, Randolph-Habecker J, Maloney DG, Andrews RG, Kiem HP, Storek J (2005) De novo generation of CD4 T cells against viruses present in the host during immune reconstitution. Blood 105:2410–2414 doi:10.1182/blood-2004-01-0348

    PubMed  CAS  Google Scholar 

  156. Sportes C, Hakim FT, Memon SA, Zhang H, Chua KS, Brown MR, Fleisher TA, Krumlauf MC, Babb RR, Chow CK, Fry TJ, Engels J, Buffet R, Morre M, Amato RJ, Venzon DJ, Korngold R, Pecora A, Gress RE, Mackall CL (2008) Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets. J Exp Med 205:1701–1714 doi:10.1084/jem.20071681

    PubMed  CAS  Google Scholar 

  157. Bolotin E, Smogorzewska M, Smith S, Widmer M, Weinberg K (1996) Enhancement of thymopoiesis after bone marrow transplant by in vivo interleukin-7. Blood 88:1887–1894

    PubMed  CAS  Google Scholar 

  158. Alpdogan O, Schmaltz C, Muriglan SJ, Kappel BJ, Perales MA, Rotolo JA, Halm JA, Rich BE, van Den Brink MR (2001) Administration of interleukin-7 after allogeneic bone marrow transplantation improves immune reconstitution without aggravating graft-versus-host disease. Blood 98:2256–2265 doi:10.1182/blood.V98.7.2256

    PubMed  CAS  Google Scholar 

  159. Mackall CL, Fry TJ, Bare C, Morgan P, Galbraith A, Gress RE (2001) IL-7 increases both thymic-dependent and thymic-independent T-cell regeneration after bone marrow transplantation. Blood 97:1491–1497 doi:10.1182/blood.V97.5.1491

    PubMed  CAS  Google Scholar 

  160. Okamoto Y, Douek DC, McFarland RD, Koup RA (2002) Effects of exogenous interleukin-7 on human thymus function. Blood 99:2851–2858 doi:10.1182/blood.V99.8.2851

    PubMed  CAS  Google Scholar 

  161. Chen BJ, Cui X, Sempowski GD, Chao NJ (2003) Growth hormone accelerates immune recovery following allogeneic T-cell-depleted bone marrow transplantation in mice. Exp Hematol 31:953–958 doi:10.1016/S0301-472X(03)00196-6

    PubMed  CAS  Google Scholar 

  162. Min D, Taylor PA, Panoskaltsis-Mortari A, Chung B, Danilenko DM, Farrell C, Lacey DL, Blazar BR, Weinberg KI (2002) Protection from thymic epithelial cell injury by keratinocyte growth factor: a new approach to improve thymic and peripheral T-cell reconstitution after bone marrow transplantation. Blood 99:4592–4600 doi:10.1182/blood.V99.12.4592

    PubMed  CAS  Google Scholar 

  163. Rossi S, Blazar BR, Farrell CL, Danilenko DM, Lacey DL, Weinberg KI, Krenger W, Hollander GA (2002) Keratinocyte growth factor preserves normal thymopoiesis and thymic microenvironment during experimental graft-versus-host disease. Blood 100:682–691 doi:10.1182/blood.V100.2.682

    PubMed  CAS  Google Scholar 

  164. Fry TJ, Moniuszko M, Creekmore S, Donohue SJ, Douek DC, Giardina S, Hecht TT, Hill BJ, Komschlies K, Tomaszewski J, Franchini G, Mackall CL (2003) IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates. Blood 101:2294–2299 doi:10.1182/blood-2002-07-2297

    PubMed  CAS  Google Scholar 

  165. Storek J, Gillespy T, Lu H, Joseph A, Dawson MA, Gough M, Morris JC, Hackman RC, Horn PA, Sale GE, Andrews RG, Maloney DG, Kiem H-P (2003) Interleukin-7 improves CD4 T cell reconstitution after autologous CD34 cell transplantation in monkeys. Blood 101:4209–4218 doi:10.1182/blood-2002-08-2671

    PubMed  CAS  Google Scholar 

  166. Lu H, Zhao Z, Kalina T, Gillespy T 3rd, Liggitt D, Andrews RG, Maloney DG, Kiem HP, Storek J (2005) Interleukin-7 improves reconstitution of antiviral CD4 T cells. Clin Immunol 114:30–41 doi:10.1016/j.clim.2004.08.008

    PubMed  CAS  Google Scholar 

  167. Beq S, Nugeyre MT, Ho Tsong Fang R, Gautier D, Legrand R, Schmitt N, Estaquier J, Barre-Sinoussi F, Hurtrel B, Cheynier R, Israel N (2006) IL-7 induces immunological improvement in SIV-infected rhesus macaques under antiviral therapy. J Immunol 176:914–922

    PubMed  CAS  Google Scholar 

  168. Seggewiss R, Lore K, Guenaga FJ, Pittaluga S, Mattapallil J, Chow CK, Koup RA, Camphausen K, Nason MC, Meier-Schellersheim M, Donahue RE, Blazar BR, Dunbar CE, Douek DC (2007) Keratinocyte growth factor augments immune reconstitution after autologous hematopoietic progenitor cell transplantation in rhesus macaques. Blood 110:441–449 doi:10.1182/blood-2006-12-065623

    PubMed  CAS  Google Scholar 

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Acknowledgment

Eddy Roosnek’s group is supported by a grant from the Swiss National Science Foundation and by the ‘Dr Henri Dubois-Ferrière-Dinu Lipatti’ Foundation.

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Authors and Affiliations

  1. Division of Hematology and Hematologic Malignancies, Department of Medicine, University of Calgary, Calgary, AB, Canada

    Jan Storek, Michelle Geddes & Faisal Khan

  2. Division of Hematology, Department of Internal Medicine, Geneva University Hospitals and University of Geneva, Geneva, Switzerland

    Bertrand Huard, Claudine Helg, Yves Chalandon, Jakob Passweg & Eddy Roosnek

  3. Division of Hematology, HUG, 24 rue Micheli-du-Crest, CH-1211, Geneva 14, Switzerland

    Eddy Roosnek

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  1. Jan Storek
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  8. Eddy Roosnek
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Correspondence to Eddy Roosnek.

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Storek, J., Geddes, M., Khan, F. et al. Reconstitution of the immune system after hematopoietic stem cell transplantation in humans. Semin Immunopathol 30, 425–437 (2008). https://doi.org/10.1007/s00281-008-0132-5

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  • DOI: https://doi.org/10.1007/s00281-008-0132-5

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