Molecular analysis of the abnormal T cell function as a pathogenesis of autoimmune diseases

T 细胞功能异常作为自身免疫性疾病发病机制的分子分析

基本信息

批准号：
03807038
负责人：
HIROHATA Shunsei
金额：
$ 1.22万
依托单位：
Teikyo University School of Medicine (1992)The University of Tokyo (1991)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

To clarify the mechanism of abnormal T cell functions in various autoimmune diseases, we have explored the nature of human suppressor T cells in several aspects. We have utilized the culture system with immobilized mAb to CD3 molecular complex, in which B cells are very potently activated through direct interactions with stimulated T cells. We have obtained the following results. First, we have demonstrated that the suppression of B cell differentiation by human suppressor T cells requires the direct interactions between ICM-1 on activated B cells and LFA-1 on suppressor T cells. Second, we have revealed that the expression of DNA polymerase alpha in B cells is inhibited by human suppressor T cells in a reversible fashion.Finally, we have disclosed that anti-CD3 activated CD4+ T cells as well as CD8+ T cells irrespective of their expression of CD45RA molecule are able to stimulate resting B cells to express IL-2 receptor (CD25), at the same time when they suppress the maturation of previously activated B cells, indicating that human activated T cells can simultaneously provide help as well as suppression irrespective of their phenotypes. It is rather suggested that the state of activation of B cells might be important in determining of functions of the activated T cells.All of these results have added novel findings to the body of knowledge about human suppressor T cells, and thus may contribute to the investigation into the pathogenesis of systemic lupus erythematous, in which the deficient suppressor T cell function plays a critical role.

为了阐明各种自身免疫性疾病中T细胞异常功能的机制，我们在几个方面探索了人类抑制T细胞的性质。我们已经使用固定的mAb对CD3分子复合物利用了培养系统，其中通过与刺激的T细胞直接相互作用，B细胞非常有效地激活B细胞。我们获得了以下结果。首先，我们已经证明，人类抑制器T细胞对B细胞分化的抑制需要ICM-1对激活的B细胞上的ICM-1与抑制T细胞上的LFA-1之间的直接相互作用。其次，我们已经揭示了B细胞中DNA聚合酶α在B细胞中的表达受到人类抑制T细胞的抑制，以可逆的方式抑制T细胞。在本文中，我们已经披露，抗CD3激活了CD4+ T细胞以及CD8+ T细胞以及CD45RA分子的表达，无法刺激静脉B的表达（CD55）。先前激活的B细胞的，表明人类活化的T细胞可以同时提供帮助和抑制，而与其表型无关。相反，有人提出，B细胞的激活状态对于确定激活的T细胞的功能可能很重要。这些结果的所有结果都增加了有关人类抑制T细胞的知识的新发现，因此可能有助于对全身性狼疮的发病机理进行研究，其中缺陷抑制T细胞T细胞T细胞t细胞功能均具有关键作用。