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Immunostimulatory versus immunosuppressive roles of IL-10 in IDDM: Analysis with IL-10—Producing transgenic NOD mice

  • Chapter
Lessons from Animal Diabetes VI

Part of the book series: Rev.Ser.Advs.Research Diab.Animals (Birkhäuser) ((RSARDA,volume 6))

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Abstract

Insulin-dependent diabetes mellitus (IDDM, type I diabetes) is an autoimmune disease resulting from autoimmune destruction of pancreatic islet B-cells. The models of human IDDM, non-obese diabetic (NOD) mice and Bio Breeding (BB) rats, have provided a large amount of information on the pathogenesis of IDDM. In these animal models, immune cells, which include helper T (CD4+) and cytotoxic T (CD8+) lymphocytes, B-lymphocytes, and macrophages, infiltrate pancreatic islets (insulitis) preceding islet B-cell destruction, with consequent overt diabetes and ketosis. Insulitis and diabetes in NOD mice or BB rats can be induced by adoptive transfer of lymphocytes and can be prevented by the immunosuppressive agents. Thus, insulitis and the consequent diabetes in NOD mice are caused by the cell-mediated organ-specific autoimmune mechanism. Although it is clear that the destructive process of islet B-cells requires both CD4+ and CD8+ T-cell subsets, the relative contribution of each subset in provoking diabetes is uncertain.

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References

  1. Mosmann TR, Cherwinski H, Bond MW, et al. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–57, 1986.

    PubMed  CAS  Google Scholar 

  2. Mosmann TR, Moore KW. The role of IL-10 in crossregulation of TH1 and TH2 responses. Immunol Today 12:A49–53, 1991.

    Article  PubMed  CAS  Google Scholar 

  3. Cherwinski HM, Schumacher JH, Brown KD, Mosmann TR. Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Thl and Th2 clones revealed by RNA hybridization, functionally monospecific bioas-says, and monoclonal antibodies. J Exp Med 166:1229–44, 1987.

    Article  PubMed  CAS  Google Scholar 

  4. Mosmann TR, Coffman RL. TH1 and TH2 cells; Different patterns of lymphokine secretion lead to different functional properties. Ann Rev Immunol 7:145–73, 1989.

    Article  CAS  Google Scholar 

  5. Mosmann TR, Coffman RL. Heterogeneity of cytokine secretion patterns and functions of helper T cells. Adv Immunol 46:111–47, 1989.

    Article  PubMed  CAS  Google Scholar 

  6. Brown KD, Zurawski SM, Mosmann TR, Zurawski G. A family of small inducible proteins secreted by leukocytes are members of a new superfamily that includes leukocyte and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes. J Immunol 142:679–87, 1989.

    PubMed  CAS  Google Scholar 

  7. Parish CR. The relationship between humoral and cell-mediated immunity. Transplant Rev 13:35–66, 1972.

    PubMed  CAS  Google Scholar 

  8. Katsura Y. Cell mediated and humoral immune responses in mice. III. Dynamic balance between delayed-type hypersensitivity and antibody response. Immunology 32:227–35, 1977.

    PubMed  CAS  Google Scholar 

  9. Cher DJ, Mosmann TR. Two types of murine helper T cell clone. II. Delayed-type hypersensitivity is mediated by Thl clones. J Immunol 138:3688–94, 1987.

    PubMed  CAS  Google Scholar 

  10. Gajewski TF, Fitch FW. Anti-proliferative effect of IFN-g in immune regulation. I. IFN-g inhibits the proliferation of Th2 but not Thl murine helper T lymphocytes clones. J Immunol 140:4245–52, 1988.

    PubMed  CAS  Google Scholar 

  11. Fernandez-Botran R, Sanders VM, Mosmann TR, Vitetta ES. Lymphokine-mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells. J Exp Med 168:543–58, 1988.

    Article  PubMed  CAS  Google Scholar 

  12. Swain SL, Weinberg AD, English M, Hutson G. IL-4 directs the development of Th2-like helper effectors. J Immunol 145:3796–806, 1990.

    PubMed  CAS  Google Scholar 

  13. Mosmann TR. Properties and functions of interleukin-10. Adv Immunol 56:1–26, 1994.

    Article  PubMed  CAS  Google Scholar 

  14. Svetic A, Jian YC, Lu P, et al.Brucella abortusinduces a novel cytokine gene expression pattern characterized by elevated IL-10 and IFN-g in CD4+T cells. Int Immunol 5:877–83, 1993.

    Article  PubMed  CAS  Google Scholar 

  15. Yamamura M, Uyemura K, Deans RJ, et al. Defining protective responses to pathogens; cytokine profiles in leprosy lesions. Science 254:277–9, 1991.

    Article  PubMed  CAS  Google Scholar 

  16. Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Thl clones. J Exp Med 170:2081–95, 1989.

    Article  PubMed  CAS  Google Scholar 

  17. Moore KW, O’Garra A, de Waal Malefyt R, et al. Interleukin-10. Ann Rev Immunol 11:165–90, 1993.

    Article  CAS  Google Scholar 

  18. Mosmann TR, Schumacher JH, Fiorentino DF, et al. Isolation of monoclonal antibodies specific for IL-4, IL-5, IL-6, and a new Th2-specific cytokine (IL-10), cytokine synthesis inhibitory factor, by using a solid phase radioimmunoadsorbent assay. J Immunol 145:2938–45, 1990.

    PubMed  CAS  Google Scholar 

  19. Yssel H, de Waal Malefyt R, Roncarolo MG, et al. IL-10 is produced by subsets of human CD4+T cell clones and peripheral blood T cells. J Immunol 149:2378–84, 1992.

    PubMed  CAS  Google Scholar 

  20. Barnes PF, Abrams JS, Lu S, et al. Patterns of cytokine production by mycobacterium-reactive human T cell clones. Infect Immun 61:197–203, 1993.

    PubMed  CAS  Google Scholar 

  21. de Waal Malefyt R, Abrams J, Bennett B, et al. Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory role of IL-10 produced by monocytes. J Exp Med 174:1209–20, 1991.

    Article  PubMed  Google Scholar 

  22. O’Garra A, Change R, Go N, et al. Ly-1 B (B-l) cells are the main source of B cell-derived interleukin 10. Eur J Immunol 22:711–17, 1992.

    Article  PubMed  Google Scholar 

  23. O’Garra A, Stapleton G, Dhar V, et al. Production of cytokines by mouse B cells: B lymphomas and normal B cells produce interleukin 10. Int Immunol 2:821–32, 1990.

    Article  PubMed  Google Scholar 

  24. Rivas JM, Ullrich SE. Systemic suppression of delayed-type hypersensitivity by supernatants from UV-irradiated keratinocytes: An essential role for keratinocyte-derived IL-10. J Immunol 149:3865–71, 1992.

    PubMed  CAS  Google Scholar 

  25. Moore KW, Vieira P, Fiorentino DF, et al. Homology of cytokines synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science 248:1230–34, 1990.

    Article  PubMed  CAS  Google Scholar 

  26. Fiorentino DF, Zlotnik A, Mosmann TR, et al. IL-10 inhibits cytokine production by activated macrophages. J Immunol 147:3815–22, 1991.

    PubMed  CAS  Google Scholar 

  27. Bogdan C, Vodovotz Y, Nathan C. Macrophage deactivation by interleukin 10. J Exp Med 174:1549–55, 1991.

    Article  PubMed  CAS  Google Scholar 

  28. Oswald IP, Gazzinelli RT, Sher A, James SL. IL-10 synergizes with IL-4 and TGF-ßto inhibit macrophage cytotoxic activity. J Immunol 148:3578–82, 1992.

    PubMed  CAS  Google Scholar 

  29. de Waal Malefyt R, Haanen J, Spits H, et al. Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression. J Exp Med 174:915–24, 1991.

    Article  PubMed  Google Scholar 

  30. Fiorentino DF, Zlotnik A, Vieira P, et al. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Thl cells. J Immunol 146:3444–51, 1991.

    PubMed  CAS  Google Scholar 

  31. Taga K, Tosato G. IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol 148:1143–48, 1992.

    PubMed  CAS  Google Scholar 

  32. Swain SL, Weinberg AD, English M. CD4+T cell subsets: Lymphokine secretion of memory cells and effector cells that develop from precursorsin vitro.J Immunol 144:1788–99, 1990.

    PubMed  CAS  Google Scholar 

  33. Hsu DH, Moore KW, Spits H. Differential effects of IL-4 and IL-10 on IL-2-induced IFN-g synthesis and lymphokine-activated killer activity. Int Immunol 4:563–9, 1992.

    Article  PubMed  CAS  Google Scholar 

  34. Go NF, Castle BE, Barrett R, et al. Interleukin 10, a novel B cell stimulatory factor: Unresponsiveness of X chromosome-linked immunodeficiency B cells. J Exp Med 172:1625–31, 1990.

    Article  PubMed  CAS  Google Scholar 

  35. Rousset F, Garcia E, Defrance T, et al. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA 89:1890–93, 1992.

    Article  PubMed  CAS  Google Scholar 

  36. Chen WF, Zlotnic A. IL-10: A novel cytotoxic T cell differentiation factor. J Immunol 147:528–34, 1991.

    PubMed  CAS  Google Scholar 

  37. Thompson-Snipes L, Dhar V, Bond MW, et al. Interleukin 10: A novel stimulatory factor for mast cells and their progenitors. J Exp Med 173:507–10, 1991.

    Article  PubMed  CAS  Google Scholar 

  38. Kikutani H, Makino S. The murine autoimmune diabetes model: NOD and related strains. Adv Immunol 51:285–322, 1992.

    Article  PubMed  CAS  Google Scholar 

  39. Makino S, Kunimoto K, Muroka Y, et al. Breeding of a non-obese, diabetic strain of mice. Exp Anim 29:1–13, 1980.

    CAS  Google Scholar 

  40. Bottazzo GF, Pujol-Borrell R, Hanafusa T. Hypothesis: Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet 2:1115–18, 1983.

    Article  PubMed  CAS  Google Scholar 

  41. Sarvetnick N, Shizuru J, Liggitt D, et al. Loss of pancreatic islet tolerance induced byβ-cell expression of interferon-g. Nature 346:844–7, 1990.

    Article  PubMed  CAS  Google Scholar 

  42. Svetic A, Jian YC, Lu P, et al.Brucella abortusinduces a novel cytokine gene expression pattern characterized by elevated IL-10 and IFN-y in CD4+T cells. Int Immunol 5:877–83, 1993.

    Article  PubMed  CAS  Google Scholar 

  43. Flesch IEA, Kaufmann SHE. Role of macrophages andabT lymphocytes in early interleukin 10 production duringListeria monocytogenesinfection. Int Immunol 6:463–8, 1994.

    Article  PubMed  CAS  Google Scholar 

  44. Katz JD, Benoist C, Mathis D. T helper cell subsets in insulin-dependent diabetes. Science 268:1185–88, 1995.

    Article  PubMed  CAS  Google Scholar 

  45. Koike T, Itoh Y, Ishi T, et al. Preventive effect of monoclonal anti-L3T4 antibody on development of diabetes in NOD mice. Diabetes 36:539–41, 1987.

    Article  PubMed  CAS  Google Scholar 

  46. Makino S, Harada M, Kishimoto Y. Absence of insulitis and overt diabetes in athymic nude mice with NOD genetic background. Exp Anim 35:495–8, 1986.

    CAS  Google Scholar 

  47. Ogawa M, Maruyama T, Hasegawa T, et al. The inhibitory effect of neonatal thymectomy on the incidence of insulitis in non-obese diabetes (NOD) mice. Biomed Res 6:103–5, 1985.

    CAS  Google Scholar 

  48. Shizuru JA, Taylor-Edwards C, Banks BA, et al. Immunotherapy of the nonobese diabetic mouse: Treatment with an antibody to T-helper lymphocytes. Science 240:659–62, 1988.

    Article  PubMed  CAS  Google Scholar 

  49. Haskin K, Mcduffie M. Acceleration of diabetes in young NOD mice with a CD4+islet-specific T cell clones. Science 249:1433–36, 1990.

    Article  Google Scholar 

  50. Nakano N, Kikutani H, Nishimoto H, Kishimoto T. T cell receptor V gene usage of islet B cell-reactive T cells is not restricted in non-obese diabetic mice. J Exp Med 173:1091–97, 1991.

    Article  PubMed  CAS  Google Scholar 

  51. Rabinovitch A. Roles of cytokines in IDDM pathogenesis and isletβ-cell destruction. Diab Rev 1:215–40, 1993.

    Google Scholar 

  52. Satoh J, Seino H, Abo T, et al. Recombinant human tumor necrosis factor a suppresses autoimmune diabetes in nonobese diabetic mice. J Clin Invest 84:1345–48, 1989.

    Article  PubMed  CAS  Google Scholar 

  53. Yokono K, Kawase Y, Nagata M, et al. Suppression of concanavalin A-induced responses in splenic lymphocytes by activated macrophages in the non-obese diabetic mice. Diabetologia 32:67–73, 1989.

    Article  PubMed  CAS  Google Scholar 

  54. Rapoport MJ, Jaramillo A, Zipris D, et al. Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice. J Exp Med 178:87–99, 1993.

    Article  PubMed  CAS  Google Scholar 

  55. Held W, Macdonald HR, Weissman IL, et al. Genes encoding tumor necrosis factor a and granzyme A are expressed during development of autoimmune diabetes. Proc Natl Acad Sci USA 87:2239–43, 1990.

    Article  PubMed  CAS  Google Scholar 

  56. Anderson JT, Cornelius JG, Jarpe AJ, et al. Insulin-dependent diabetes in the NOD mouse model. II.ßcell destruction in autoimmune diabetes is a TH2 and not a TH1 mediated event. Autoimmunity 15:113–22, 1993.

    Article  PubMed  CAS  Google Scholar 

  57. Jarpe AJ, Hickman MR, Anderson JT, et al. Flow cytometric enumeration of mononuclear cell populations infiltrating the islets of Langerhans in prediabetic NOD mice: Development of a model of autoimmune insulitis for type I diabetes. Reg Immuol 3:305–17, 1991.

    CAS  Google Scholar 

  58. Guberski DL, Thomas VA, Shek WR, et al. Induction of type I diabetes by Kilham’s rat virus in diabetes-resistant BB/Wor rats. Science 254:1010–13, 1991.

    Article  PubMed  CAS  Google Scholar 

  59. Fujita H, Fujino H, Nonaka K, Tarui S. Retrovirus-like particles in pancreaticβ-cells of NOD mice. Biomed Res 5:67–70, 1984.

    Google Scholar 

  60. Rabinovitch A. Immunoregulatory and cytokine imbalances in the pathogenesis of IDDM: Therapeutic intervention by immunostimulation? Diabetes 43:613–21,1994.

    Article  PubMed  CAS  Google Scholar 

  61. Leiter EH. The role of environmental factors in modulating insulin-dependent diabetes. In: Current topics in immunology and microbiology: The role of microorganisms in non-infectious disease, de Vries R, Cohen I, Van Rood JJ, eds. Springer-Verlag, Berlin, pp 39–55, 1990.

    Google Scholar 

  62. Tisch R, Yang X-D, Singer SM, et al. Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature 366:72–5,1993.

    Article  PubMed  CAS  Google Scholar 

  63. Muir A, Peck A, Clara-Salzler M, et al. Insulin immunization of nonobese diabetic mice induces a protective insulitis characterized by diminished intraislet interferon-g transcription. J Clin Invest 95:628–34, 1995.

    Article  PubMed  CAS  Google Scholar 

  64. Mcdaniel ML, Hughes JH, Wolf BA, et al. Descriptive and mechanistic considerations of interleukin 1 and insulin secretion. Diabetes 37:1311–15, 1988.

    Article  PubMed  CAS  Google Scholar 

  65. Mandrup-Poulsen T, Bendtzen K, Nielsen JH, et al. Cytokines cause functional and structural damage to isolated islets of Langerhans. Allergy 40:424–9, 1985.

    Article  PubMed  CAS  Google Scholar 

  66. Pukel C, Baquerizo H, Rabinovitch A, et al. Destruction of rat islet cell monolayers by cytokines: Synergistic interaction of interferon-g, tumor necrosis factor, lymphotoxin, and interleukin 1. Diabetes 37:133–6, 1988.

    Article  PubMed  CAS  Google Scholar 

  67. Jacob CO, Aiso S, Michie SA, Mevitt HO. Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): Similarities between TNF-a and interleukin 1. Proc Natl Acad Sci USA 87:968–72, 1990.

    Article  PubMed  CAS  Google Scholar 

  68. Seino H, Takahashi K, Satoh J, et al. Prevention of autoimmune diabetes with lymphotoxin in NOD mice. Diabetes 42:398–404, 1993.

    Article  PubMed  CAS  Google Scholar 

  69. Serreze DV, Hamaguchi K, Leiter EH. Immunostimulation circumvents diabetes in NOD/Lt mice. J Autoimmun 2:759–76, 1989.

    Article  PubMed  CAS  Google Scholar 

  70. Pennline KJ, Roque-Gaffney E, Monahan M. Recombinant human IL-10 prevents the onset of diabetes in the nonobese diabetic mouse. Clin Immunol Immunopathol 71:169–75, 1994.

    Article  PubMed  CAS  Google Scholar 

  71. Allison J, McClive P, Oxbrow L, et al. Genetic requirements for acceleration of diabetes in non-obese diabetic mice expressing interleukin-2 in isletβ-cells. Eur J Immunol 24:2535–11, 1994.

    Article  PubMed  CAS  Google Scholar 

  72. Wogensen L, Lee MS, Sarvetnick N. Production of interleukin 10 by islet cells accelerates immune-mediated destruction ofβcells in nonobese diabetic mice. J Exp Med 179:1379–84, 1994.

    Article  PubMed  CAS  Google Scholar 

  73. Moritani M, Yoshimoto K, Tashiro F, et al. Transgenic expression of IL-10 in pancreatic islet A cells accelerates autoimmune insulitis and diabetes in non-obese diabetic mice. Int Immunol 6:1927–36, 1994.

    Article  PubMed  CAS  Google Scholar 

  74. Yang XD, Tisch R, Singer ST, et al. Effect of tumor necrosis factor a on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process. J Exp Med 180:995–1004, 1994.

    Article  PubMed  CAS  Google Scholar 

  75. Sarvetnick N, Liggitt D, Pitts SL, et al. Insulin-dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-gamma. Cell 52:773–82, 1988.

    Article  PubMed  CAS  Google Scholar 

  76. Stewart TA, Hultgren B, Huang X, et al. Induction of type I diabetes by interferonαin transgenic mice. Science 260:1942–46, 1993.

    Article  PubMed  CAS  Google Scholar 

  77. Higuchi Y, Herreta P, Munies P, et al. Expression of a tumor necrosis factorαtrans-gene in murine panceratic B cells results in severe and permanent insulitis without evolution towards diabetes. J Exp Med 176:1719–31, 1992.

    Article  PubMed  CAS  Google Scholar 

  78. Picarella D, Kratz A, Li C, et al. Transgenic tumor necrosis fcator (TNF)-αproduction in pancreatic islets leads to insulitis, not diabetes; Distinct patterns of inflammation in TNF-αand TNF-βtransgenic mice. J Immunol 150:4136–50, 1993.

    PubMed  CAS  Google Scholar 

  79. Heath WR, Allison J, Hoffmann MW, et al. Autoimmune diabetes as a consequence of locally produced interleukin-2. Nature 359:547–9, 1992.

    Article  PubMed  CAS  Google Scholar 

  80. Wogensen L, Huang X, Sarvetnick N. Leukocyte extravasation into the pancreatic tissue in transgenic mice expressing interleukin 10 in the islets of Langerhans. J Exp Med 178:175–185, 1993.

    Article  PubMed  CAS  Google Scholar 

  81. Allison J, Campbell IL, Morahan G, et al. Diabetes in transgenic mice resulting from over-expression of class I histocompatibility molecules in pancreatic B cells. Nature 333:529–33, 1988.

    Article  PubMed  CAS  Google Scholar 

  82. Lo D, Burkly LC, Widera G, et al. Diabetes and tolerance in transgenic mice expressing class II MHC molecules in pancreatic beta cells. Cell 53:159–68, 1988.

    Article  PubMed  CAS  Google Scholar 

  83. Allison J, Malcolm L, Culvenor J, et al. Over expression ofβ 2-microglobulin in transgenic mouse isletβcells results in defective insulin secretion. Proc Natl Acad Sci USA 88:2070–74, 1991.

    Article  PubMed  CAS  Google Scholar 

  84. Efrat S, Fleisher N, Hanahan D. Diabetes induces in male transgenic mice by expression of human H-ras oncoprotein in pancreaticβcells. Mol Cell Biol 10:1779–83, 1990.

    PubMed  CAS  Google Scholar 

  85. Epstein PN, Overbeek PA, Means AR. Calmodulin-induces early-onset diabetes in transgenic mice. Cell 58:1067–73, 1989.

    Article  PubMed  CAS  Google Scholar 

  86. Lee MS, Wogensen L, Shizuru J, et al. Pancreatic islet production of murine interleukin-10 does not inhibit immune-mediated tissue destruction. J Clin Invest 93:1332–38, 1994.

    Article  PubMed  CAS  Google Scholar 

  87. Sedelain MWJ, Qin HY, Lauzon J, Singh B. Prevention of type I diabetes in NOD mice by adjuvant immunotherapy. Diabetes 39:583–9, 1990.

    Article  Google Scholar 

  88. Bach JF. Insulin-dependent diabetes mellitus as an autoimmune disease. Endocr Rev 15:516–42, 1994.

    PubMed  CAS  Google Scholar 

  89. Hasegawa Y, Yokono K, Taki T, et al. Prevention of autoimmune insulin-dependent diabetes in non-obese diabetic mice by anti-LFA-1 and anti-ICAM-1 mAb. Int Immunol 6:831–8, 1994.

    Article  PubMed  CAS  Google Scholar 

  90. Kawakami Y, Yamaoka T, Hirochica R, et al. Somatic gene therapy for diabetes with an immunological safety system for complete removal of transplanted cells. Diabetes 41:956–61, 1992.

    Article  PubMed  CAS  Google Scholar 

  91. Yoshimoto K, Murakami R, Moritani M, et al. Loss of ganciclovir sensitivity by exclusion by thymidine kinase gene from transplanted proinsulin-producing fibroblasts as a gene therapy model for diabetes. Gene Therapy, in press.

    Google Scholar 

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Authors and Affiliations

  1. Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Tokushima 770, Japan

    Mitsuo Itakura MD, PhD, Maki Moritani, Katsuhiko Yoshimoto & Satoshi Otsuka

  2. Department of Molecular Embryology Institute of Development, Aging and Cancer, Tohoku University, 980-77, Sendai, Japan

    Chikara Hashimoto & Jun-Ichi Miyazaki

  3. Department of Pathology, School of Medicine, The University of Tokushima, Tokushima 770, Japan

    Toshiaki Sano

  4. Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Kuramoto, Tokushima-city 770, Japan

    Mitsuo Itakura MD, PhD

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  1. Mitsuo Itakura MD, PhD
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  1. Department of Biochemistry, Hadassah Medical Center, POB 12000, IL 91120, Jerusalem, Israel

    Eleazar Shafrir

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© 1996 Birkhäuser Boston

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Itakura, M. et al. (1996). Immunostimulatory versus immunosuppressive roles of IL-10 in IDDM: Analysis with IL-10—Producing transgenic NOD mice. In: Shafrir, E. (eds) Lessons from Animal Diabetes VI. Rev.Ser.Advs.Research Diab.Animals (Birkhäuser), vol 6. Birkhäuser Boston. https://doi.org/10.1007/978-1-4612-4112-6_11

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  • DOI: https://doi.org/10.1007/978-1-4612-4112-6_11

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