REGULATION OF AUTOIMMUNITY TO GAD65 IN IDDM

1型糖尿病或IDDM是一种严重的自身免疫性疾病 成千上万的美国人。它的特征是一种攻击 在胰腺，这会抑制胰岛素的产生。在攻击的同时 浸润液包括多种细胞类型，T细胞是关键。这个 T细胞的确切靶点也可能是多方面的，但在其中， 最重要的是谷氨酸脱羧酶(GAD)， 尤其是65kD形式，GAD65。试验性给药 重组GAD对非肥胖糖尿病(NOD)小鼠的作用 易患IDDM，改善对胰腺的攻击，以及 随后的疾病发展。这些和其他结果都有 促使美国食品和药物管理局审查 对IDDM高危人群实施GAD治疗。 尽管如此，目前对 GAD的自动反应性。特别是，目前还不清楚为什么会点头 小鼠和(通过外推)易患IDDM的人类未能 自然地产生对GAD的耐受性。《红楼梦》的特点 对GAD65的自身反应性可以通过开发 携带GAD65和/或T细胞抗原T的NOD小鼠新品系 GAD65的细胞抗原受体以不寻常的方式表达。 这样的小鼠也有助于研究T细胞如何对GAD产生自身反应 可以由其他淋巴细胞和微生物调节 环境。这类小鼠的发育过程在 建议，并为他们的详细研究提供了案例。

Type 1 diabetes or 'IDDM' is a severe autommune disease afflicting hundreds of thousands of Americans. It is characterized by an attack on the pancreas, that abrogates insulin production. While the attacking infiltrate comprises multiple cell types, T cells are critical. The precise target of the T cells may also be manifold, but among them, central importance is attached to glutamic acid decarboxylase (GAD), particularly the 65kD form, GAD65. Experimental administration of recombinant GAD to non obese diabetic (NOD) mice that are highly predisposed to IDDM, ameliorated the attack on the pancreas, and subsequent disease development. These and other results have prompted the Food and Drug Administration to review the idea of administering GAD to individuals at high risk for developing IDDM. This notwithstanding, there is currently very little understanding of autoreactivity to GAD. In particular, it remains unclear why NOD mice and (by extrapolation) humans predisposed to IDDM fail to develop tolerance to GAD naturally. The characterization of the autoreactivity to GAD65 can be facilitated by the development of novel strains of NOD mouse in which GAD65 and/or T cell antigen T cell antigen receptors to GAD65, are expressed in unusual patterns. Such mice also facilitate the study of how T cells autoreactive to GAD can be regulated by other lymphocytes, and by the microbial environment. The development of such mice is described in the proposal and the case made for their detailed study.