| Project/Area Number |
61480251
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Kobe University |
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Principal Investigator |
BABA Shigeaki Kobe University School of Medicine, Professor, 医学部, 教授 (10030818)
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| Co-Investigator(Kenkyū-buntansha) |
YOKONO Koichi Kobe University Medical Hospital, Assistant Professor, 医学部附属病院, 助手 (50144580)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1986: ¥5,600,000 (Direct Cost: ¥5,600,000)
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| Keywords | Type I diabetes / Anti-islet cell surface antibodies / NOD mouse / Activated macrophages / Interleukin 2 / サプレッサーT細胞 / 自己免疫疾患 / 膵ラ島炎 / ヘルパーTリンパ球 / サプレッサーTリンパ球 / 細胞傷害性Tリンパ球 / 単クローン性抗体 / 免疫抑制療法 / Tリンパ球 / マクロファージ |
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| Research Abstract |
We have investigated the pathological analysis of various humoral and ellular immune abnormalities in Type I diabetes using nonbese diabetic (NOD) mice. Monoclonal anti-islet cell surface antibodies (ICSA) were produced by hybridization 6 spleen lymphocytes from NOD mice. These monoclonal antibodies recognized 64K and 105K dalton cell surface proteins in cultured insulinoma ells, showed the antibody-dependent cellular cytotoxicity to insulinoma cells, and inhibited the insulin release from isolated pancreatic islets. In addition, the administration of antiserum to these monoclonal antibodies into NOD mice could prevent the occurrence and the sevirity of pancreatic insulitis.
In the cellular immune abnormalities, we found that activated macrophages existing among the spleen cells could suppress the response of splenic T cells to their mitogens. Furthermore, suppressor T cell activity was already depressed in NOD mice before diabetes began. A substantial decrease in the number of suppressor T cells and the impaired expression of interleukin 2 receptors on these cells may explain this depressed suppressor activity. This impairment may contribute to the hyperimmunity in NOD mice which could induce and continue the autoimmune phenomenon concerning the pathogenesis of Type I diabetes. Finally, we have recently established the presence of cytotoxic T lymphocytes (CTL) specific for islet cells in NOD mice, suggesting that CTL are directly involved in the destruction of pancreatic islet cells in this animal model.
These studies in the NOD mouse suggest that several humoral and cellular immune abnormalities appear to participate directly or indirectly in the destruction of beta cells in Type I diabetes.
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