Immunologic Research

, Volume 33, Issue 1, pp 23–34 | Cite as

Immunologic states of autoimmune diseases

  • Toru Abo
  • Toshihiko Kawamura
  • Hisami Watanabe


The etiology and immunologic states of autoimmune diseases have mainly been discussed without consideration of extrathymic T cells, which exist in the liver, intestine, and excretion glands. Because extrathymic T cells are autoreactive and are often simultaneously activated along with autoantibody-producing B-1 cells, these extrathymic T cells and B-1 cells should be introduced when considering the immunologic states of autoimmune diseases. The immunologic states of autoimmune diseases resemble those of aging, chronic GVH disease, and malarial infection. Namely, under all these conditions, conventional T and B cells are rather suppressed concomitant with thymic atrophy or involution. In contrast, extrathymic T cells and B-1 cells are inversely activated at this time. These facts suggest that the immunologic states of autoimmune diseases should be revaluated by introducing the concept of extrathymic T cells and autoantibody-producing B-1 cells, which might be primordial lymphocytes in phylogeny.

Key Words

Autoimmune disease Extrathymic T cells Autoreactivity B-1 cells Immunosuppression 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Guy-Grand D, Cerf-Bensussan N, Malissen B, Malassis-Seris M, Briottet C, Vassalli P: Two gut intraepithelial CD8+ lymphocyte populations with different T cell receptors: a role for the gut epithelium in T cell differentiation. J Exp Med 1991;173:471.PubMedCrossRefGoogle Scholar
  2. 2.
    Rocha B, Vassalli P, Guy-Grand D: The V beta repertoire of mouse gut homodimeric alpha CD8 intraepithelial T cell receptor alpha/beta+ lymphocytes reveals a major extrathymic pathway of T cell differentiation. J Exp Med 1991;173:483.PubMedCrossRefGoogle Scholar
  3. 3.
    Abo T, Ohteki T, Seki S, et al.: The appearance of T cells bearing self-reactive T cell receptor in the livers of mice injected with bacteria. J Exp Med 1991;174:417.PubMedCrossRefGoogle Scholar
  4. 4.
    Sato K, Ohtsuka K, Hasegawa K, et al.: Evidence for extrathymic generation of intermediate T cell receptor cells in the liver revealed in thymectomized, irradiated mice subjected to bone marrow transplantation. J Exp Med 1995;182:759.PubMedCrossRefGoogle Scholar
  5. 5.
    Kappler JW, Roehm N, Marrack P: T cell tolerance by clonal elimination in the thymus. Cell 1987;49:273–280.PubMedCrossRefGoogle Scholar
  6. 6.
    MacDonald HR, Schneider R, Lees RK, et al.: T-cell receptor V beta use predicts reactivity and tolerance to Mlsa-encoded antigens. Nature 1988;332:40.PubMedCrossRefGoogle Scholar
  7. 7.
    Finkel TH, Cambier JC, Kubo RT, Born WK, Marrack P, Kappler JW: The thymus has two functionally distinct populations of immature alpha beta+ T cells: one population is deleted by ligation of alpha beta TCR. Cell 1989;58:1047.PubMedCrossRefGoogle Scholar
  8. 8.
    Kawachi Y, Watanabe H, Moroda T, et al.: Self-reactive T cell clones in a restricted population of interleukin-2 receptor β+ cells expressing intermediate levels of the T cell receptor in the liver and other immune organs. Eur J Immunol 1995;25:2272.PubMedCrossRefGoogle Scholar
  9. 9.
    Moroda T, Iiai T, Kawachi Y, Kawamura T, Hatakeyama K, Abo T: Restricted appearance of self-reactive clones into intermediate T cell receptor cells in neonatally thymectomized mice with autoimmune disease. Eur J Immunol 1996;26:3084.PubMedCrossRefGoogle Scholar
  10. 10.
    Naito T, Kawamura T, Bannai M, et al.: Simultaneous activation of natural killer T cells and autoantibody production in mice injected with denatured syngeneic liver tissue. Clin Exp Immunol 2002;129:397.PubMedCrossRefGoogle Scholar
  11. 11.
    Morshed SRM, Mannoor K, Halder RC, et al.: Tissue-specific expansion of NKT and CD5B cells at the onset of autoimmune disease in (NZB×NZW)F1 mice. Eur J Immunol 2002;32:2551.PubMedCrossRefGoogle Scholar
  12. 12.
    Mannoor MK, Halder RC, Morshed SRM, et al.: Essential role of extrathymic T cells in protection against malaria. J Immunol 2002;169:301.PubMedGoogle Scholar
  13. 13.
    Wang S, Li C, Kawamura H, Watanabe H, Abo T: Unique sensitivity to α-galactosylceramide of NKT cells in the uterus. Cell Immunol 2002;215:98.PubMedCrossRefGoogle Scholar
  14. 14.
    Arai K, Yamamura S, Hanyu T, et al.: Extrathymic differentiation of resident T cells in the joints of mice with collagen-induced arthritis. J Immunol 1996;157:5170.PubMedGoogle Scholar
  15. 15.
    Narita J, Kawamura T, Miyaji C, et al.: Abundance of NKT cells in the salivary glands but absence there of in the liver and thymus of aly/aly mice with Sjögren syndrome. Cell Immunol 1999;192:149.PubMedCrossRefGoogle Scholar
  16. 16.
    Kantor AB, Merrill CE, Herzenberg LA, Hillson JL: An unbiased analysis of V[H]-D-J[H] sequences from B-1a, B-1b, and conventional B cells. J Immunol 1997;158: 1175.PubMedGoogle Scholar
  17. 17.
    Ochi H, Takeshita H, Suda T, Nisitani S, Honjo T, Watanabe T: Regulation of B-1 cell activation and its autoantibody production by Lyn kinase-regulated signalling. Immunology 1999;98:595.PubMedCrossRefGoogle Scholar
  18. 18.
    Abo T, Watanabe H, Sato K et al.: Extrathymic T cells stand at an intermediate phylogenetic position between natural killer cells and thymus-derived T cells. Nat Immun 1995;14:173.PubMedGoogle Scholar
  19. 19.
    Watanabe H, Miyaji C, Kawachi Y, et al.: Relationships between intermediate TCR cells and NK1.1. +T cells in various immune organs. NK1.1 +T cells are present within a population of intermediate TCR cells. J Immunol 1995;155:2972.PubMedGoogle Scholar
  20. 20.
    Maruyama S, Tsukahara A, Suzuki S, et al.: Quick recovery in the generation of self-reactive CD4low NKT cells by an alternative intrathymic pathway when restored from acute thymic atrophy. Clin Exp Immunol 1999;117:587.PubMedCrossRefGoogle Scholar
  21. 21.
    Emoto M, Mittrücker H-W, Schmits R, Mak TW, Kaufmann SHE: Critical role of leukocyte function-associated antigen-1 in liver accumulation of CD4NKT cells. J Immunol 1995;162:5094.Google Scholar
  22. 22.
    Hammond K, Cain W, Van Driel I, Godfrey D: Three day neonatal thymectomy selectively depletes NK 1.1 +T cells. Int Immunol 1998;10:1491.PubMedCrossRefGoogle Scholar
  23. 23.
    Tilloy F, Di Santo JP, Bendelac A, Lantz O: Thymic dependence of invariant V α14+ natural killer-T cell development. Eur J Immunol 1999;29:3313.PubMedCrossRefGoogle Scholar
  24. 24.
    Coles MC, Raulet DH: NK1.1+T cells in the liver arise in the thymus and are selected by interactions with class I molecules on CD4 +CD8+ cells. J Immunol 2000; 164:2412.PubMedGoogle Scholar
  25. 25.
    Kameyama H, Kawamura T, Naito T, et al.: Size of the population of CD4+ natural killer T cells in the liver is maintained without supply by the thymus during adult life. Immunology 2001;104:135.PubMedCrossRefGoogle Scholar
  26. 26.
    Minagawa M, Oya H, Yamamoto S, et al.: Intensive expansion of natural killer T cells in the early phase of hepatocyte regeneration after partial hepatectomy in mice and its association with sympathetic nerve activation. Hepatology 2000;31:907.PubMedCrossRefGoogle Scholar
  27. 27.
    Miyaji C, Watanabe H, Miyakawa R, et al.: Identification of effector cells for TNFα-mediated cytotoxicity against WEHI164S cells. Cell Immunol 2002;216:43.PubMedCrossRefGoogle Scholar
  28. 28.
    Weerasinghe A, Sekikawa H, Watanabe H, et al.: Association of intermediate T cell receptor cells, mainly their NK1.1 subset, with protection from malaria. Cell Immunol 2001;207:28.PubMedCrossRefGoogle Scholar
  29. 29.
    Mannoor MK, Weerasinghe A, Halder RC, et al.: Resistance to malarial infection is achieved by the cooperation of NK1.1+ and NK1.1 subsets of intermediate TCR cells which are constituents of innate immunity. Cell Immunol 2001;211:96.PubMedCrossRefGoogle Scholar
  30. 30.
    Kawano T, Junqing C, Koezuka Y, et al.: CD1d-restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides. Science 1997;278:1626.PubMedCrossRefGoogle Scholar
  31. 31.
    Burdin N, Brossary L, Koezuka Y, et al.: Selective ability of mouse CD1 to present glycolipids: α-Galactosyl-ceramide specifically stimulates V α14+NK T lymphocytes. J Immunol 1998;161:3271.PubMedGoogle Scholar
  32. 32.
    Brossary L, Naidenko O, Burdin N, Matsuda J, Sakai T, Kronenberg M: Structural requirements for galactosyl-ceramide recognition by CD1-restricted NK T cells. J Immunol 1998;161:5124.Google Scholar
  33. 33.
    Osman Y, Kawamura T, Naito T, et al.: Activation of hepatic NKT cells and subsequent liver injury following administration of α-galactosyl ceramide. Eur J Immunol 2000;30:1919.PubMedCrossRefGoogle Scholar
  34. 34.
    Kawabe S, Abe T, Kawamura H, Gejyo F, Abo T: Generation of B220low B cells and production of autoantibodies in mice with experimental amyloidosis: association of primordial T cells with this phenomenon. Clin Exp Immunol 2004;135:200.PubMedCrossRefGoogle Scholar
  35. 35.
    Segal BM, Shevach EM: IL-12 unmasks latent autoimmune disease in resistant mice. J Exp Med 1996;184:771.PubMedCrossRefGoogle Scholar
  36. 36.
    Takeda K, Dennert G: The development of autoimmunity in C57BL/6 1 pr mice correlated with the disappearance of natural killer type 1-positive cells: evidence of their suppressive action on bone marrow stem cell proliferation, B cell immunoglobulin secretion, and autoimmune symptoms. J Exp Med 1993;177:155.PubMedCrossRefGoogle Scholar
  37. 37.
    Wilson SB, Kent SC, Patton KT, et al.: Extreme Th1 bias of invariant Valpha24JalphaQ T cells in type 1 diabetes. Nature 1998;391:177.PubMedCrossRefGoogle Scholar
  38. 38.
    Godfrey DI, Kinder SJ, Silvera P, Baxter AG: Flow cytometric study of T cell development in NOD mice reveals a deficiency in αβTCR+CD4CD8 thymocytes. J Autoimmun 1997;10:279.PubMedCrossRefGoogle Scholar
  39. 39.
    Baxter AG, Kinder SJ, Hammond KJ, Scollay R, Godfrey DI: Association between αβTCR+CD4CD8 T-cell deficiency and IDDM in NOD/Lt mice. Diabetes 1997;46:572.PubMedCrossRefGoogle Scholar
  40. 40.
    Lehuen A, Lantz O, Beaudoin L, et al.: Overexpression of natural killer T cells protects Vα14-Jα281 transgenic nonobese diabetic mice against diabetes. J Exp Med 1998;188:1831.PubMedCrossRefGoogle Scholar
  41. 41.
    Ferguson A: Intraepithelial lymphocytes of the small intestine. Gut 1977;18:921.PubMedGoogle Scholar
  42. 42.
    Guy-Grand D, Griscelli C, Vassalli P: The mouse gut T lymphocyte, a novel type of T cell. J Exp Med 1978; 148:1661.PubMedCrossRefGoogle Scholar
  43. 43.
    De Geus B, Van den Enden M, Coolen C, Nagelkerken L, Van der Heijden P, Rozing J: Plienotype of intraepithelial lymphocytes in euthymic and athymic mice: implications for differentiation of cells bearing a CD3-associatedγδT cell receptor. Eur J Immunol 1990;20:291.PubMedCrossRefGoogle Scholar
  44. 44.
    Bandeira A, Itohara S, Bonneville M, et al.: Extrathymic origin of intestinal intraepithelial lymphocytes bearing T-cell antigen receptor γδ. Proc Natl Acad Sci USA 1991;88:43.PubMedCrossRefGoogle Scholar
  45. 45.
    Rocha B, Vassali P, Guy-Grand D: The extrathymic T-cell development pathway. Immunol Today 1992;13:449.PubMedCrossRefGoogle Scholar
  46. 46.
    Ohtsuka K, Iiai T, Watanabe H, et al.: Similarities and differences between extrathymic T cells residing in mouse liver and intestine. Cell Immunol 1994;153:52.PubMedCrossRefGoogle Scholar
  47. 47.
    Ohtsuka K, Hasegawa K, Yamagiwa S, et al.: Intraepithelial lymphocytes in colon have similar properties to intraepithelial lymphocytes in small intestine and hepatic intermediate TCR cells. Digest Dis Sci 1996;41:902.PubMedCrossRefGoogle Scholar
  48. 48.
    Bannai M, Kawamura T, Naito T, et al.: Abundance of unconventional CD8+ natural killer T cells in the large intestine. Eur J Immunol 2001;31:3361.PubMedCrossRefGoogle Scholar
  49. 49.
    Yamagiwa S, Sugahara S, Shimizu T, et al.: The primary site of CD48B220+T cells inlpr mice; the appendix in normal mice. J Immunol 1998;160:2665.PubMedGoogle Scholar
  50. 50.
    Takii Y, Hashimoto S, Iiai T, Watanabe H, Hatakeyama K, Abo T: Increase in the proportion of granulated CD56+T cells in patients with malignancy. Clin Exp Immunol 1994;97:522.PubMedGoogle Scholar
  51. 51.
    Okada T, Iiai T, Kawachi Y, et al.: Origin of CD57+ T cells which increase at tumour sites in patients with colorectal cancer. Clin Exp Immunol 1995;102:159.PubMedGoogle Scholar
  52. 52.
    Arai K, Yamamura S, Seki S, Hanyu T, Takahashi HE, Abo T: Increase of CD57+ T cells in knee joints and adjacent bone marrow of rheumatoid arthritis (RA) patients: implication for an anti-inflammatory role. Clin Exp Immunol 1998;111:345.PubMedCrossRefGoogle Scholar
  53. 53.
    Miyaji C, Watanabe H, Toma H, et al.: Functional alteration of granulocytes, NK cells, and natural killer T cells in centenarians. Human Immunol 2000;61:908.CrossRefGoogle Scholar
  54. 54.
    Iiai T, Watanabe H, Suda T, Okamoto H, Abo T, Hatakeyama K: CD161+ T (NT) cells exist predominantly in human intestinal epithelium as well as in liver. Clin Exp Immunol 2002;129:92.PubMedCrossRefGoogle Scholar
  55. 55.
    Watanabe H, Weerasinghe A, Miyaji C, et al.: Expansion of unconventional T cells with natural killer markers in malaria patients. Parasitol Int 2003;52:61.PubMedCrossRefGoogle Scholar
  56. 56.
    Norris S, Collins C, Doherty DG, et al.: Resident hepatic lymphocytes are phenotypically different from circulating lymphocytes. J Hepatol 1998;28:84.PubMedCrossRefGoogle Scholar
  57. 57.
    Doherty DG, Norris S, Madrigal-Estebas L, et al.: The human liver contains multiple populations of NK cells, T cells, and CD3+CD56+ natural T cells with distinct cytotoxic activities and Th1, Th2, and Th0 cytokine secretion patterns. J Immunol 1999;163:2314.PubMedGoogle Scholar
  58. 58.
    Hilbe W, Eisterer W, Schmid C, et al.: Bone marrow lymphocyte subsets in myelodysplastic syndromes. J Clin Pathol 1994;47:505.PubMedCrossRefGoogle Scholar
  59. 59.
    Gorochov G, Debre P, Leblond V, Sadat-Sowti B, Sigaux F, Autran B: Oligoclonal expansion of CD8+CD57+ T cells with restricted T-cell receptor β chain variability after bone marrow transplantation Blood 1994;83:587.PubMedGoogle Scholar
  60. 60.
    Autran B, Leblond V, Sadat-Sowti B, et al.: A soluble factor released by CD8+CD57+ lymphocytes from bone marrow transplanted patients inhibits cell-mediated cytolysis. Blood 1991;77:2237.PubMedGoogle Scholar
  61. 61.
    Tsuchida M, Hashimoto M, Abo T, Miyamura H, Hirano T, Eguchi S: CD5+B cells in the thymus of patients with myasthenia gravis. Biomed Res 1993;14:19.Google Scholar
  62. 62.
    Ohteki T, Seki S, Abo T, Kumagai K: Liver is a possible site for the proliferation of abnormal CD3+48 double-negative lymphocytes in autoimmune MRL lpr/lpr mice. J Exp Med 1990;172:7.PubMedCrossRefGoogle Scholar
  63. 63.
    Iiai T, Kimura M, Kawachi Y, et al.: Characterization of intermediate T-cell-receptor cells expanding in the liver, thymus and other organs in autoimmune lpr mice: parallel analysis with their normal counterparts. Immunology 1995;85:601.Google Scholar
  64. 64.
    Yamagiwa S, Kuwano Y, Hasegawa K, et al.: Existence of a small population of IL-2Rβhi TCRint cells in SCG and MRL-lpr/lpr mice which produce normal Fas mRNA and Fas molecules from the lpr gene. Eur J Immunol 1996;26:1409.PubMedCrossRefGoogle Scholar
  65. 65.
    Xavier RM, Yamauchi Y, Nakamura M, et al.: Antinuclear antibodies in healthy aging people: a prospective study. Mech Ageing Dev 1995;78:145.PubMedCrossRefGoogle Scholar
  66. 66.
    Tomer Y, Shoenfeld Y: Ageing and autoantibodies. Autoimmunity 1988;1:141.PubMedGoogle Scholar
  67. 67.
    Rose NR: Thymus function, ageing and autoimmunity. Immunol Lett 1994;40:225.PubMedCrossRefGoogle Scholar
  68. 68.
    Brill S, Globerson A: Autoimmunity and aging. Isr J Med Sci 1988;24:732.PubMedGoogle Scholar
  69. 69.
    Kay MM: Autoimmunity and aging. Concepts Immunopathol 1988;6:166.PubMedGoogle Scholar
  70. 70.
    Tomer Y, Shoenfeld Y: The significance of natural autoantibodies. Immunol Invest 1988;17:389.PubMedGoogle Scholar
  71. 71.
    Miyaji C, Watanabe H, Toma H, et al.: Functional alteration of granulocytes, NK cells, and natural killer T cells in centenarians. Human Immunol 2000;61:908.CrossRefGoogle Scholar
  72. 72.
    Gleichmann E, Pals ST, Rolink AG, Radaszkiewicz T, Gleichmann H: Graft-versus-host reactions: clues to the etiopathology of a spectrum of immunological diseases. Immunol Today 1984;5:324.CrossRefGoogle Scholar
  73. 73.
    Via CS, Shearer GM: T-cell interactions in autoimmunity: insights from a murine model of graft-versus-host disease. Immunol Today 1988;9:207.PubMedCrossRefGoogle Scholar
  74. 74.
    Meyers CM, Tomaszewski JE, Glass JD, Chen CW: The nephritogenic T cell response in murine chronic graftversus-host disease. J Immunol 1998;161:5321.PubMedGoogle Scholar
  75. 75.
    Okamoto I, Kohno K, Tanimoto T, et al.: IL-18 prevents the development of chronic graft-versus-host disease in mice. J Immunol 2000;164:6067.PubMedGoogle Scholar
  76. 76.
    Kawamura T, Kawachi Y, Kuwano Y, et al.: Mechanisms involved in Graft-versus-Host disease induced by the disparity of minor histocompatibility Mls antigens. Scand J Immunol 1999;49:258.PubMedCrossRefGoogle Scholar
  77. 77.
    Halder RC, Kawamura T, Bannai M, et al.: Intensive generation of NK1.1 extrathymic T cells in the liver by injection of bone marrow cells isolated from mice with a mutation of polymorphic major histocompatibility complex antigens. Immunology 2001;102:450.PubMedCrossRefGoogle Scholar
  78. 78.
    Wenisch C, Wenisch H, Bankl HC, et al.: Detection of anti-neutrophil cytoplasmic antibodies after acute Plasmodium falciparum malaria. Clin Diagn Lab Immunol 1996;3:132.PubMedGoogle Scholar
  79. 79.
    Lloyd CM, Collins I, Belcher AJ, Manuelpillai N, Wozencraft AO, Staines NA: Characterization and pathological significance of monoclonal DNA-binding antibodies from mice with experimental malaria infection. Infect Immun 1994;62:1982.PubMedGoogle Scholar
  80. 80.
    Ribeiro CD, Alfred C, Monjour L, Gentilini M: Normal frequency of anti-thyroglobulin antibodies in hyperendemic areas of malaria: relevance to the understanding of autoantibody formation in malaria. Trop Geogr Med 1984;36:323.Google Scholar
  81. 81.
    Kataaha PK, Facer CA, Mortazavi-Milani SM, Stierle H, Holborow EJ: Stimulation of autoantibody production in normal blood lymphocytes by malaria culture supernatants. Parasite Immunol 1984;6:481.PubMedGoogle Scholar
  82. 82.
    Ribeiro CT, De Roquefeuil S, Druilhe P, Monjour L, Homberg JC, Gentilini M: Abnormal anti-single stranded (ss) DNA activity in sera from Plasmodium falciparum infected individuals Trans R Soc Trop Med Hyg 1984;78:742.CrossRefGoogle Scholar
  83. 83.
    Kawamura T, Toyabe S, Moroda T, et al.: Neonatal granulocytosis is a postpartum event which is seen in the liver as well as in the blood. Hepatology 1997;26:1567.PubMedCrossRefGoogle Scholar
  84. 84.
    Maruyama S, Minagawa M, Shimizu T, et al.: Administration of glucocorticoids markedly increases the numbers of granulocytes and extrathymic T cells in the bone marrow. Cell Immunol 1999;194:28.PubMedCrossRefGoogle Scholar
  85. 85.
    Shimizu T, Kawamura T, Miyaji T, et al.: Resistance of extrathymic T cells to stress and the role of endogenous glucocorticoids in stress associated immuno suppression. Scand J Immunol 2000;51:285.PubMedCrossRefGoogle Scholar
  86. 86.
    Abo T, Kawamura T, Watanabe H: Physiological responses of extrathymic T cells in the liver. Immunol Rev 2000;174:135.PubMedCrossRefGoogle Scholar
  87. 87.
    Minagawa M, Oya H, Yamamoto S, et al.: Intensive expansion of natural killer T cells in the early phase of hepatocyte regeneration after partial hepatectomy in mice and its association with sympathetic nerve activation. Hepatology 2000;31:907.PubMedCrossRefGoogle Scholar
  88. 88.
    Oya H, Kawamura T, Shimizu T, et al.: The differential effect of stress on natural killer T and NK cell function. Clin Exp Immunol 2000;121:384.PubMedCrossRefGoogle Scholar
  89. 89.
    Kato T, Sato Y, Takahashi S, Kawamura H, Hatakeyama K, Abo T: Involvement of natural killer T cells and granulocytes in the inflammation induced by partial hepatectomy. J Hepatol 2004;40:285.PubMedCrossRefGoogle Scholar
  90. 90.
    Kawabe S, Abe T, Kawamura H, Gejyo F, Abo T: Generation of B220low B cells and production of autoantibodies in mice with experimental amyloidosis: association of primordial T cells with this phenomenon. Clin Exp Immunol 2004;135:200.PubMedCrossRefGoogle Scholar
  91. 91.
    Tsukahara A, Tada T, Suzuki S, et al.: Adrenergic stimulation simultaneously induces the expansion of granulocytes and extrathymic T cells in mice. Biomed Res 1997;18:237.Google Scholar
  92. 92.
    Kawamura T, Miyaji C, Toyabe S, Fukuda M, Watanabe H, Abo T: Suppressive effect of anti ulcer agents on granulocytes—a role for granulocytes in gastric ulcer formation. Digest Dis Sci 2000;45:1786.PubMedCrossRefGoogle Scholar
  93. 93.
    Kato T, Sato Y, Takahashi S, Kawamura H, Hatakeyama K, Abo T: Involvement of natural killer T cells and granulocytes in the inflammation induced by partial hepatectomy. J Hepatol 2004;40:285.PubMedCrossRefGoogle Scholar
  94. 94.
    Schwartz M, Cohen IR: Autoimmunity can benefit self-maintenance. Immunol Today 2000;21:265.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  1. 1.Division of Cellular and Molecular Immunology, Center of Molecular BiosciencesUniversity of RyukyusOkinawaJapan
  2. 2.Department of ImmunologyNiigata University School of MedicineNiigataJapan

Personalised recommendations