Studies on the mechanisms of autoimmune diabetes and prevension of the disease in NOD mice.

• Project/Area Number: 05454207
• Research Category: Grant-in-Aid for General Scientific Research (B)
• Allocation Type: Single-year Grants
• Research Field: Immunology
• Research Institution: Osaka University
• Principal Investigator: KIKUTANI Hitoshi Osaka Univ., Inst.Mol.Cell.Biol., Assoc.Prof., 細胞生体工学センター, 助教授 (80161412)
• Project Period (FY): 1993 – 1994
• Project Status: Completed (Fiscal Year 1994)
• Budget Amount: ¥6,900,000 (Direct Cost: ¥6,900,000); Fiscal Year 1994: ¥1,800,000 (Direct Cost: ¥1,800,000); Fiscal Year 1993: ¥5,100,000 (Direct Cost: ¥5,100,000)
• Keywords: T cell / Autoimmunity / MHC class II antigen / Autoantigen / NOD mouse / Type I diabetes / 自己免疫疾患 / 組織適合性抗原

Research Abstract

The following experiments were carried out using NOD mouse to elucidate the mechanisms of development of autoimmunity.
1. Self antigens recognized by 5 autoreactive T cell clones from NOD mice were characterized. All these clones reacted with antigens that were rapidly released from pancreatic islet cells. Two of these T cell clones were found to recognized distinct epitopes.
2. We also attempted to transfer diabetes to NOD-scid using T cell clones. All the clones could transfer insulitis to NOD-scid. However, diabetes could be transfered only when a mixture of these clones were injected to NOD-scid.
3. Previously, I-E transgenes could prevent diabetes of NOD mice. However, when spleen cells of I-E NOD mice were transfered to NOD-scid, development of diabetes was observed. This indicates that autoreactive T cells may exist but their activity may be suppressed in I-E NOD mice.
4. Glutamic acid decarboxylase (GAD) is one of candidates of diabetogenic antigens. To determine that GAD is really diabetogenic, GAD transgenic mice were produced.

Research Products

• [Publications] Nagasawa,T.H.Kikutani,T.Kishimoto.: "Molecular cloning and structure of a novel pre-B growth stimulating factor(PBSF)." Proc.Natl Acad.Sci.,USA. 91. 2305-2309 (1994)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nagasawa,T.,T.Kaisro,H.Kikutani,et al.: "Generation and characterization of a monoclonal antibody the inhibits stromal cell-dependent B lymphopoiesis." J.Immunol.152. 2788-2797 (1994)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kawabe,T.,T.Naka,H.Kikutani,et al.: "The immune responses in CD40-deficient mice:Impaired immunoglobulin class switching and germinal center formation." Immunity. 1. 167-178 (1994)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Fujiwara,H.,H.Kikutani,et al.: "The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice." Proc.Natl.Acad.Sci.,USA. 91. 6835-6839 (1994)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Davey,E.J.,H.Kikutani,et al.: "Homotypic aggregation of murine B lymphocytes is independent of CD23." Eur.J.Immunol.in press. (1995)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yukawa,K.,T.Yasui,H.Kikutani,et al.: "Epoc-1:a POU-domain gene expressed in murine epidermal basal cslls and thymic stromal cells." Gene. 133. 163-169 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Nagasawa, T., H.Kikutani, and T.Kishimoto.: "Molecular cloning and structure of a novel pre-B growth stimulating factor (PBSF)." Proc.Natl.Acad.Sci., USA. 91. 2305-2307 (1994)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nagasawa, T., T.Kaishio, T.Kishimoto, and H.Kikutani.: "Generation and characterization of monoclonal antibody that inhibits stromal celldependent B lymphopoiesis." J.Immunol.152. 2788-1797 (1994)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kawabe, T., T.Naka, K.Yoshida, T.Tanaka, H.Fujiwara, S.Suematsu, N.Yoshida, T.Kishimoto, and H.Kikutani: "The immune responses in CD40-deficient mice : Impaired immunoglobulin class switching and germinal center formation." Immunity. 1. 167-178 (1994)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Fujiwara, H., H.Kikutani, S.Suematsu, T.Naka, K.Oshida, K.Yoshida, T.Tanaka, M.Suemura, N.Matsumoto, S.Kojima, T.Kishimoto, and N.Yoshida.: "The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice." Proc.Natl.Acad.Sci., USA. 91. 6835-6839 (1994)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Davey, E.J., W.C.Bartlett, H.Kikutani, H.Fujiwara, T.Kishimoto, D.H.Conrad, and E.Severinson.: "Homotypic aggregation of murine B lymphocytes in independent of CD23." Eur.J.Immunol.(in press). (1995)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yukawa, K., T.Yasui, A.Yamamoto, H.Shiku, T.Kishimoto and H.Kikutani: "Epoc-1 : a POU-domain gene expressed in murine epidermal basal cells and tymic stromal cells." Gene. 133. 163-169 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nagasawa,T.,H.Kikutani,and T.Kishimoto: "Molecular cloning and structure of a novel pre-B growth stimulating factor(PBSF)." Porc.Natl.Acad.Sci.,USA. 91. 2305-2309 (1994)
• [Publications] Nagasawa,T.,T.Kaisho,H.Kikutani,et al.: "Generation and characterization of a monoclonal anitbody that inhibits stromal cell-dependent B lymphopoiesis." J.Immunol.152. 2788-2797 (1994)
• [Publications] Kawabe,T.,T.Naka,H.Kikutani,et al.: "The immune responses in CD40-deficient mice:Impaired immunoglobulin class switching and germinal center formation." Immunity.1. 167-178 (1994)
• [Publications] Fujiwara,H.,H.Kikutani,et al.: "The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice." Proc.Natl.Acad.Sci.,USA. 91. 6835-6839 (1994)
• [Publications] Davey,E.J.,H.Kikutani,et al.: "Homotypic aggregation of murine B lymphocytes is independent of CD23." Eur.J.Immunol.(in press). (1995)
• [Publications] Yukawa,K.,T.Yasui,H.Kikutani,et al.: "Epoc-l:a POU-domain gene expressed in murine epidermal basal cells and thymic stromal cells." Gene. 133. 163-169 (1993)
• [Publications] Nagasawa,T.,H.Kikutani,and T.Kishimoto: "Molecular cloning and structure of a novel pre-B growth stimulating factor(PBSF)." Proc.Natl.Acad.Sci.,USA. (in press). (1994)
• [Publications] Nagasawa,T.,T.Kaisho,H.Kikutani,et al.: "Generation and characterization of a monoclonal antibody that inhibits stromal cell-dependent B lymphopoiesis." J.Immunol.(in press). (1994)
• [Publications] Fujiwara,H.,H.Kikutani,S.Suematsu et al.: "The absence of IgE antibody-mediated augmentation of immune responses in CD23-deficient mice." Proc.Natl.Acad.Sci.,USA. (in press). (1994)