International Journal of Hematology

, Volume 78, Issue 3, pp 188–194 | Cite as

Immunoregulatory Cells for Transplantation Tolerance and Graft-versus-Leukemia Effect

  • Masahiro Imamura
  • Junji Tanaka
Progress in Hematology


Various immunoregulatory cells that inhibit graft-versus-host disease (GVHD) and induce the graft-versus-leukemia (GVL) effect are found after allogeneic hematopoietic stem cell transplantation. These cells comprise CD4+CD25+ regulatory T-cells, regulatory dendritic cells (rDCs), γδ T-cells, natural killer (NK) T-cells, and NK cells and T-cells with inhibitory NK receptors. Although the first 4 types of cells effectively inhibit GVHD in animal models, with rDCs showing an inhibitory effect on GVHD in humans as well, the GVL effect was observed only in rDCs. Additional analyses are required to determine whether these cells can inhibit GVHD and exert the GVL effect in humans. In contrast, NK cells and T-cells with inhibitory NK receptors have been shown in humans to possess a suppressive activity against GVHD while preserving the GVL effect. These results indicate that immunoregulatory cells may be used to modulate GVHD and the GVL effect in clinical settings.Int J Hematol. 2003;78:188-194.

Key words

Graft-versus-host disease Graft-versus-leukemia effect Immunoregulatory cells Hematopoietic stem cell transplantation 


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  1. 1.
    Thomas ED, Storb R, Clift RA, et al. Bone marrow transplantation (second of two parts).N Engl J Med. 1975;292:895–902.CrossRefPubMedGoogle Scholar
  2. 2.
    Kernan N, Collins NH, Juliano L, Cartagena T, Dupont B, O’Reilly RJ. Clonable T-lymphocytes in T-cell-depleted bone marrow transplants correlate with development of graft-versus-host disease.Blood. 1986;68:770–773.PubMedGoogle Scholar
  3. 3.
    Dokhelar M, Wiels J, Lipinski M, et al. Natural killer cell activity in human bone marrow recipients: early reappearance of peripheral natural killer activity in graft-versus-host disease.Transplantation. 1981;31:61–65.CrossRefPubMedGoogle Scholar
  4. 4.
    Kappler JW, Roehm N, Marrack P. T cell tolerance by clonal elimination in the thymus.Cell. 1987;49:273–280.CrossRefPubMedGoogle Scholar
  5. 5.
    Dallman MJ, Wood KJ, Hamano K, et al. Cytokines and peripheral tolerance to alloantigen.Immunol Rev. 1993;133:5–18.CrossRefPubMedGoogle Scholar
  6. 6.
    Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation.Blood. 1990;75:555–562.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Cohen JL, Trenado A, Vasey D, Klatzmann D, Salomon BL. CD4+CD25+ immunoregulatory T cells: new therapeutics for graft-versus-host disease.J Exp Med. 2003;196:401–406.CrossRefGoogle Scholar
  8. 8.
    Shevach EM, McHugh RS, Piccirillo CA, Thornton AM. Control of T-cell activation by CD4+CD25+ suppressor T cells.Immunol Rev. 2001;182:58–67.CrossRefPubMedGoogle Scholar
  9. 9.
    Cederbom L, Hall H, Ivars F. CD4+CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells.Eur J Immunol. 2000;30:1538–1543.CrossRefPubMedGoogle Scholar
  10. 10.
    Takahashi T, Tagami T, Yamazaki S, et al. Immunologic self-tolerance maintained by CD25+CD4+ regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4.J Exp Med. 2000;192:303–310.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Nakamura K, Kitani A, Strober W. Cell contact-dependent immunosuppression by CD4+CD25+ regulatory T cells is mediated by cell surface-bound transforming growth factor β.J Exp Med. 2001;194:629–644.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Hara M, Kingsley CI, Niimi M, et al. IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo.J Immunol. 2001;166:3789–3796.CrossRefPubMedGoogle Scholar
  13. 13.
    Gregori S, Casorati M, Amuchastegui S, Smiroldo S, Davalli AM, Adorini L. Regulatory T cells induced by 1α, 25-dihydroxyvitamin D3 and mycophenolate mofetil treatment mediate transplantation tolerance.J Immunol. 2001;167:1945–1953.CrossRefPubMedGoogle Scholar
  14. 14.
    Johnson BD, Konkol MC, Truitt RL. CD25+ immunoregulatory T-cells of donor origin suppress alloreactivity after BMT.Biol Blood Marrow Transplant. 2002;8:525–535.CrossRefPubMedGoogle Scholar
  15. 15.
    Taylor PA, Friedman TM, Korngold R, Noelle RJ, Blazar BR. Tolerance induction of alloreactive T cells via ex vivo blockade of the CD40:CD40L costimulatory pathway results in the generation of a potent immune regulatory cell.Blood. 2002;99:4601–4609.CrossRefPubMedGoogle Scholar
  16. 16.
    Taylor PA, Lees CJ, Blazar BR. The infusion of ex vivo activated and expanded CD4+CD25+ immune regulatory cells inhibits graft- versus-host disease lethality.Blood. 2002;99:3493–3499.CrossRefPubMedGoogle Scholar
  17. 17.
    Hoffman P, Ermann J, Edinger M, Fathman CG, Strober S. Donor- type CD4+CD25+ regulatory T cells suppress lethal acute graft- versus-host disease after allogeneic bone marrow transplantation.J Exp Med. 2003;196:389–399.CrossRefGoogle Scholar
  18. 18.
    Banchereau J, Steinman RM. Dendritic cells and the control of immunity.Nature. 1998;392:245–252.CrossRefPubMedGoogle Scholar
  19. 19.
    Caramalho I, Lopes-Carvalho T, Ostler D, Zelenay S, Haury M, Demengeot J. Regulatory T cells selectively express Toll-like receptors and are activated by lipopolysaccharide.J Exp Med. 2003;197:403–411.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sachs DL. CD4+CD25+ regulatory T cells controlLeishmania major persistence and immunity.Nature. 2002;420:502–507.CrossRefPubMedGoogle Scholar
  21. 21.
    Sakaguchi S. Control of immune responses by naturally arising CD4+ regulatory T cells that express toll-like receptors.J Exp Med. 2003;197:397–401.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3.Science. 2003;299:1057–1061.CrossRefPubMedGoogle Scholar
  23. 23.
    Yamagiwa S, Gray JD, Hashimoto S, Horwitz DA. A role for TGF-β in the generation and expansion of CD4+CD25+ regulatory T cells from human peripheral blood.J Immunol. 2001;166:7282–7289.CrossRefPubMedGoogle Scholar
  24. 24.
    Thornton AM, Shevach EM. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production.J Exp Med. 1998;188:287–296.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Vella AT, Dow S, Potter TA, Kappler J, Marrack P. Cytokine- induced survival of activated T cells in vitro and in vivo.Proc Natl Acad Sci USA. 1998;95:3810–3815.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Groux H, O’Garra A, Bigler M, et al. CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis.Nature. 1997;389:737–742.CrossRefPubMedGoogle Scholar
  27. 27.
    Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G. Ex vivo isolation and characterization of CD4+CD25+ T cells with regulatory properties from human blood.J Exp Med. 2001;193:1303–1310.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Bhandoola A, Tai X, Eckhaus M, et al. Peripheral expression of self-peptide-MHC-II influences the reactivity and self-tolerance of mature CD4+ T cells: evidence from a lymphopenic T-cell model.Immunity. 2002;17:425–436.CrossRefPubMedGoogle Scholar
  29. 29.
    Min W-P, Zhou D, Ichim TE, et al. Inhibitory feedback loop between tolerogenic dendritic cells and regulatory T cells in transplant tolerance.J Immunol. 2003;170:1304–1312.CrossRefPubMedGoogle Scholar
  30. 30.
    Jonuleit H, Schmitt E, Steinbrink K, Enk AH. Dendritic cells as a tool to induce anergic and regulatory T cells.Trends Immunol. 2001;22:394–400.CrossRefPubMedGoogle Scholar
  31. 31.
    Roncarolo MG, Levings MK, Traversari C. Differentiation of T regulatory cells by immature dendritic cells.J Exp Med. 2001;193:F5-F9.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Frasca L, Scotta C, Lombardi G, Piccolella E. Human anergic CD4+ T cells can act as suppressor cells by affecting autologous dendritic cell conditioning and survival.J Immunol. 2002;168:1060–1068.CrossRefPubMedGoogle Scholar
  33. 33.
    Sato K, Yamashita N, Yamashita N, Baba M, Matsuyama T. Regulatory dendritic cells protect mice from acute graft-versus-host disease and leukemia relapse.Immunity. 2003;18:367–379.CrossRefPubMedGoogle Scholar
  34. 34.
    Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH. Induction of interleukin 10-producing, nonproliferating CD4+ T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells.J Exp Med. 2000;192:1213–1222.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Steinbrink K, Wolfl M, Jonuleit H, Knop J, Enk AH. Induction of tolerance by IL-10-treated dendritic cells.J Immunol. 1997;159:4772–4780.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Sato K, Yamashita N, Matsuyama T. Human peripheral blood monocyte-derived interleukin-10-induced semi-mature dendritic cells induce anergic CD4+ and CD8+ T cells via presentation of the internalized soluble antigen and cross-presentation of the phagocytosed necrotic cellular fragments.Cell Immunol. 2002;215:186–194.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Penna G, Adorini L. la,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation.J Immunol. 2000;164:2405–2411.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Blazar BR, Taylor PA, Panoskalysis-Mortari A, et al. Lethal murine graft-versus-host disease induced by donor γδ expressing T cells with specificity for host nonclassical major histocompatibility complex class Ib antigens.Blood. 1996;87:827–837.PubMedPubMedCentralGoogle Scholar
  39. 39.
    Tsuji S, Char D, Bucy RP, Simonsen M, Chen CH, Cooper MD. 78 T cells are secondary participants in acute graft-versus-host reactions initiated by CD4+ αβ T cells.Eur J Immunol. 1996;26:420–427.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Ellison CA, MacDonald GC, Rector ES, Gartner JG. γδ T cells in the pathobiology of murine acute graft-versus-host disease: evidence that γδ T cells mediate natural killer-like cytotoxicity in the host and that elimination of those cells from donors significantly reduces mortality.J Immunol. 1995;155:4189–4198.PubMedGoogle Scholar
  41. 41.
    Shiohara T, Moriya N, Hayakawa J, Itohara S, Ishikawa H. Resistance to cutaneous graft-versus-host disease is not induced in T cell receptor δ gene mutant mice.J Exp Med. 1996;183:1483–1489.CrossRefPubMedGoogle Scholar
  42. 42.
    Drobyski WR, Majewski D, Hanson G. Graft facilitating doses of ex vivo activated γδ T cells do not cause lethal murine graft versus host disease.Biol Blood Marrow Transplant. 1999;5:222–230.CrossRefPubMedGoogle Scholar
  43. 43.
    Mombaerts P, Arnoldi J, Russ F, Tonegawa S, Kaufmann SH. Different roles of αβ and γδ T cells in immunity against an intracellular pathogen.Nature. 1993;365:53–56.CrossRefPubMedGoogle Scholar
  44. 44.
    Welsh RM, Lin M-Y, Lohman BL, Varga SM, Zarozinski CC, Selin LK. αβ and γδ T-cell networks and their roles in natural resistance to viral infections.Immunol Rev. 1997;159:79–93.CrossRefPubMedGoogle Scholar
  45. 45.
    Ke Y, Pearce K, Lake JP, Ziegler HK, Kapp JA. γδ T lymphocytes regulate the induction and maintenance of oral tolerance.J Immunol. 1997;158:3610–3618.PubMedGoogle Scholar
  46. 46.
    Born W, Cady C, Jones-Carson J, Mukasa A, Lahn M, O’Brien R. Immunoregulatory functions of γδ T cells.Adv Immunol. 1999;71:77–144.CrossRefPubMedGoogle Scholar
  47. 47.
    Lahn M, Kanehiro A, Takeda K, et al. Negative regulation of airway responsiveness that is dependent on γδ T cells and independent of αβ T cells.Nat Med. 1999;5:1150–1156.CrossRefPubMedGoogle Scholar
  48. 48.
    Fu Y-X, Roark CE, Kelley K, et al. Immune protection and control of inflammatory tissue necrosis by γδ T cells.J Immunol. 1994;153:3101–3115.PubMedGoogle Scholar
  49. 49.
    D’Souza CD, Cooper AM, Frank A, Mazzaccaro RJ, Bloom BR, Orme IM. An anti-inflammatory role for γδ T lymphocytes in acquired immunity toMycobacterium tuberculosis.J Immunol. 1997;158:1217–1221.PubMedGoogle Scholar
  50. 50.
    Drobyski WR, Vodanovic-Jankovic S, Klein J. Adoptively transferred γδ T cells indirectly regulate graft-versus-host reactivity following donor leukocyte infusion therapy in mice.J Immunol. 2000;165:1634–1640.CrossRefPubMedGoogle Scholar
  51. 51.
    MacDonald HR. NK1.1+ T cell receptor-α/β+ cells: new clues to their origin, specificity, and function.J Exp Med. 1995;182:633–638.CrossRefPubMedGoogle Scholar
  52. 52.
    Bendelac A, Rivera MN, Park SH, Roark JH. Mouse CD1-specific NK1 T cells: development, specificity, and function.Annu Rev Immunol. 1997;15:535–562.CrossRefPubMedGoogle Scholar
  53. 53.
    Eberl G, Lees R, Smiley ST, Taniguchi M, Grusby MJ, MacDonald HR. Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells.J Immunol. 1999;162:6410–6419.PubMedGoogle Scholar
  54. 54.
    Hammond KJ, Pelikan SB, Crowe NY, et al. NKT cells are pheno- typically and functionally diverse.Eur J Immunol. 1999;29:3768–3781.CrossRefPubMedGoogle Scholar
  55. 55.
    Arase H, Arase N, Ogasawara K, Good RA, Onoe K. An NK1.1+ CD4+CD8- single-positive thymocyte subpopulation that expresses a highly skewed T-cell antigen receptor family.Proc Natl Acad Sci USA. 1992;89:6506–6510.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Lanz O, Bendelac A. An invariant T cell receptor α chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice.J Exp Med. 1994;180:1097–1106.CrossRefGoogle Scholar
  57. 57.
    Makino Y, Kanno R, Ito T, Higashino K, Taniguchi M. Predominant expression of invariant Vα14+ TCR α chain in NK1.1+ T cell populations.Int Immunol. 1995;7:1157–1161.CrossRefPubMedGoogle Scholar
  58. 58.
    Ohteki T, MacDonald HR. Stringent Vβ requirement for the development of NK1.1+ T cell receptor-αβ+ cells in mouse liver.J Exp Med. 1996;183:1277–1282.CrossRefPubMedGoogle Scholar
  59. 59.
    Kawano T, Cui J, Koezuka Y, et al. CD1d-restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides.Science. 1997;278:1626–1629.CrossRefPubMedGoogle Scholar
  60. 60.
    Yoshimoto T, Paul WE. CD4+, NK1.1+ T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3.J Exp Med. 1994;179:1285–1295.CrossRefPubMedGoogle Scholar
  61. 61.
    Shi FD, Flodstrom M, Balasa B, et al. Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse.Proc Natl Acad Sci USA. 2001;98:6777–6782.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Wang B, Geng YB, Wang CR. CD1-restricted NK T cells protect nonobese diabetic mice from developing diabetes.J Exp Med. 2001;194:313–320.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Hong S, Wilson MT, Serizawa I, et al. The natural killer T-cell ligand α-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice.Nat Med. 2001;7:1052–1056.CrossRefPubMedGoogle Scholar
  64. 64.
    Sharif S, Arreaza GA, Zucker P, et al. Activation of natural killer T cells by α-galactosylceramide treatment prevents the onset and recurrence of autoimmune type 1 diabetes.Nat Med. 2001;7:1057–1062.CrossRefPubMedGoogle Scholar
  65. 65.
    Rigby SM, Rouse T, Field EH. Total lymphoid irradiation nonmyeloablative preconditioning enriches for IL-4-producing CD4+-TNK cells and skews differentiation of immunocompetent donor CD4+ cells.Blood. 2003;101:2024–2032.CrossRefPubMedGoogle Scholar
  66. 66.
    Fowler DH, Gress RE. Th2 and Tc2 cells in the regulation of GVHD, GVL, and graft rejection: considerations for the allogeneic transplantation therapy of leukemia and lymphoma.Leuk Lymphoma. 2000;38:221–234.CrossRefPubMedGoogle Scholar
  67. 67.
    Lan F, Zeng D, Higuchi M, Huie P, Higgins JP, Strober S. Predominance of NK1.1+ TCR αβ+ or DX5+TCR αβ+ T cells in mice conditioned with fractionated lymphoid irradiation protects against graft-versus-host disease: “natural suppressor” cells.J Immunol. 2001;167:2087–2096.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Ljunggren HG, Karre K. In search of the ‘missing self’: MHC molecules and NK cell recognition.Immunol Today. 1990;11:237–244.CrossRefPubMedGoogle Scholar
  69. 69.
    Biassoni R, Falco M, Cambiaggi A, et al. Amino acid substitutions can influence the natural killer (NK)-mediated recognition of HLA-C molecules: role of serine-77 and lysine-80 in the target cell protection from lysis mediated by “group 2” and “group 1” NK clones.J Exp Med. 1995;182:605–609.CrossRefPubMedGoogle Scholar
  70. 71.
    Bordignon C, Daley JP, Nakamura I. Hematopoietic histocompatibility reactions by NK cells in vitro: model for genetic resistance to marrow grafts.Science. 1985;23:1398–1401.CrossRefGoogle Scholar
  71. 72.
    Imamura M, Tsutsumi Y, Miura Y, Toubai T, Tanaka J. Immune reconstitution and tolerance after allogeneic hematopoietic stem cell transplantation.Hematology. 2003;8:19–26.CrossRefPubMedGoogle Scholar
  72. 73.
    Tanaka J, Mori A, Ohta S, et al. Expression of HLA-C-specific natural killer cell receptors (CD158a and CD158b) on peripheral blood mononuclear cells after allogeneic bone marrow transplantation.Br J Haematol. 2000;108:778–783.CrossRefPubMedGoogle Scholar
  73. 74.
    Tanaka J, Tutumi Y, Zhang L, et al. Increased proportion of HLA- class-I-specific natural killer cell receptors (CD94) on peripheral blood mononuclear cells after allogeneic bone marrow transplantation.Acta Haematol. 2001;105:89–91.CrossRefPubMedGoogle Scholar
  74. 75.
    Tanaka J, Tutumi Y, Mori A, et al. Sequential analysis of HLA-C- specific killer cell inhibitory receptor (CD158b) expressing peripheral blood mononuclear cells during chronic graft-versus-host disease.Bone Marrow Transplant. 2000;26:287–290.CrossRefPubMedGoogle Scholar
  75. 76.
    Moretta A, Biassoni R, Bottino C, et al. Major histocompatibility complex class I-specific receptors on human natural killer and T lymphocytes.Immunol Rev. 1997;155:105–117.CrossRefPubMedGoogle Scholar
  76. 77.
    Braud VM, Allan DSJ, O’Callaghan CA, et al. HLA-E binds to natural killer cell receptor CD94/NKG2A, B and C.Nature. 1998;391:795–799.CrossRefPubMedGoogle Scholar
  77. 78.
    McMahon CW, Raulet DH. Expression and function of NK-cell receptors in CD8+T cells.Curr Opin Immunol. 2001;13:465–470.CrossRefPubMedGoogle Scholar
  78. 79.
    Braud VM, Aldemir H, Breart B, Ferlin WG. Expression of CD94- NKG2A inhibitory receptor is restricted to a subset of CD8+ T cells.Trends Immunol. 2003;24:162–164.CrossRefPubMedGoogle Scholar
  79. 80.
    Jabri B, Selby JM, Negulescu H, et al. TCR specificity dictates CD94/NKG2A expression by human CTL.Immunity. 2002;17:487–499.CrossRefPubMedGoogle Scholar
  80. 81.
    Borrego F, Kabat J, Sanni TB, Colligan JE. NK-cell CD94/NKG2A inhibitory receptors are internalized and recycle independently of inhibitory signaling processes.J Immunol. 2002;169:6102–6111.CrossRefPubMedGoogle Scholar
  81. 82.
    Groh V, Wu J, Yee C, Spies T. Tumor-derived soluble MIC ligands impair expression of NKG2D and T-cell activation.Nature. 2002;419:734–738.CrossRefPubMedGoogle Scholar
  82. 83.
    Anfossi N, Pascal V, Vivier E, Ugolini S. Biology of T memory type 1 cells.Immunol Rev. 2001;181:269–278.CrossRefPubMedGoogle Scholar
  83. 84.
    Gunturi A, Berg RE, Forman J. Preferential survival of CD8 T and NK cells expressing high levels of CD94.J Immunol. 2003;170:1737–1745.CrossRefPubMedGoogle Scholar
  84. 85.
    Tanaka J, Tutumi Y, Li Z, et al. Induction of CD94/NKG2A expression on T cells in mixed lymphocyte culture by CD14+ cells from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells.Br J Haematol. 2002;117:751–754.CrossRefPubMedGoogle Scholar
  85. 86.
    Albi N, Ruggeri L, Aversa F, et al. Natural killer (NK)-cell function and antileukemic activity of a large population of CD3+/CD8+ T cells expressing NK receptors for major histocompatibility complex class I after “three-loci” HLA-incompatible bone marrow transplantation.Blood. 1996;87:3993–4000.PubMedGoogle Scholar
  86. 87.
    Aversa F, Tabilio A, Velardi A, et al. Treatment of high risk leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype.N Engl J Med. 1998;339:1186–1193.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 88.
    Ruggeri L, Capanni M, Urbani E, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants.Science. 2002;295:2097–3100.CrossRefPubMedGoogle Scholar
  88. 89.
    Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25): breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.J Immunol. 1995;155:1151–1164.PubMedGoogle Scholar
  89. 90.
    Zocchi MR, Ferrarini M, Rugarli C. Selective lysis of the autologous tumor by δTCS1+γδ+ tumor-infiltrating lymphocytes from human lung carcinomas.Eur J Immunol. 1990;20:2685–2689.CrossRefPubMedGoogle Scholar
  90. 91.
    Taniguchi M, Harada M, Kojo S, Nakayama T, Wakao H. The regulatory role of Vα14 NKT cells in innate and acquired.Annu Rev Immunol. 2003;21:483–513.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2003

Authors and Affiliations

  1. 1.Department of Hematology and OncologyHokkaido University Graduate School of MedicineSapporoJapan

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