Defects in deletional tolerance of CD8+ T cells in autoimmune diabetes.
Defects in deletional tolerance of CD8+ T cells in autoimmune diabetes.
复制标题
自身免疫性糖尿病中 CD8 T 细胞的缺失耐受性缺陷。
DOI：
10.1159/000060533
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Sherman,LA
中科院分区：
文献类型：
--
作者：
Kreuwel,HT;Sherman,LA
Type 1 diabetes mellitus (T1D) is a T-cell-mediated autoimmune disease, characterized by the destruction of insulin-producing pancreatic ẞ cells. In humans, this disease occurs in children and young adults and is often referred to as juvenile diabetes. One of the best rodent models for T1D is the nonobese diabetic mouse (NOD)[1-4]. In diabetic patients and NOD mice, immunohistological studies of pancreata reveal the presence of both CD4+ and CD8+ T cells, suggesting a role for CD8+ T cells in disease [5-10]. Studies of disease progression in the NOD mouse model have confirmed that CD8+ T cells play an important role [11-17]. The elimination of CD8+ T cells either through the use of in vivo depleting antibodies, or by producing NOD mice deficient in MHC class I (β2-microglobulin knockout mice) that lack functional CD8+ T cells, results in the inhibition of autoimmune diabetes [18-22]. Also, ẞ-islet-specific CD8+ T cells have been isolated from NOD mice that have a direct pathogenic effect upon adoptive transfer into nondiabetic recipients [17, 23]. Here, we will consider the possibility that defects in the deletion of high-affinity CD8+ T cells specific for B-cell antigens may contribute to autoimmune diabetes. Before considering this issue, it is helpful to review what is currently known about how CD8+ T-cell tolerance to peripheral antigens is normally established and its potential role in averting autoimmunity.
