Role of antigen-presenting cells in mediating tolerance and autoimmunity
Role of antigen-presenting cells in mediating tolerance and autoimmunity
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DOI：
10.1084/jem.191.11.2021
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发表时间：
2000-06-05
影响因子：
15.3
通讯作者：
Ohashi, PS
中科院分区：
文献类型：
--
作者：
Garza, KM;Chan, SM;Ohashi, PS
决定受体刺激是否导致淋巴细胞耐受或激活的机制仍然知之甚少。我们使用大鼠胰岛素启动子(RIP)-gp/P14双转基因小鼠，在胰岛细胞上表达淋巴细胞性脉毛膜脑膜炎病毒（LCMV）糖蛋白（gp），并与表达LCMV-gp特异性T细胞受体的T细胞一起评估诱导自身免疫的需求。我们的研究表明，通过激活标记上调和诱导效应细胞毒性活性，gp肽gp33的施用导致p14转基因T细胞的激活。这种治疗也会导致P14 T细胞的扩增和缺失。尽管多肽能诱导细胞毒性T淋巴细胞活性，但并不足以诱导糖尿病。然而，gp肽与活化的抗cd40抗体一起施用可迅速诱导糖尿病。这些发现表明，耐受性对自身免疫的诱导是由静止的抗原提呈细胞和活化的抗原提呈细胞决定的。
The mechanisms that determine whether receptor stimulation leads to lymphocyte tolerance versus activation remain poorly understood. We have used rat insulin promoter (RIP)-gp/P14 double-transgenic mice expressing the: lymphocytic choriomeningitis virus (LCMV) glycoprotein (gp) on pancreatic beta-islet: cells together with T cells expressing an LCMV-gp-specific T cell receptor to assess the requirements for the induction of autoimmunity. Our studies have shown that administration of the gp peptide gp33 leads to the activation of P14-transgenic T cells, as measured by the upregulation of activation markers and the induction of effector cytotoxic activity. This treatment also leads to expansion and deletion of P14 T cells. Despite the induction of cytotoxic T lymphocyte activity, peptide administration is not sufficient to induce diabetes. However, the administration of gp peptide together with an activating anti-CD40 antibody rapidly induces diabetes. These findings suggest that the induction of tolerance versus autoimmunity is determined by resting versus activated antigen-presenting cells.