Guerder S, Meyerhoff J, Flavell R
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011.
Immunity. 1994 May;1(2):155-66. doi: 10.1016/1074-7613(94)90109-0.
T cell tolerance to peripheral antigens is believed to result mainly from the inability of parenchymal cells to present antigens in an immunogenic form due to the lack of expression of T cell costimulator. We found, however, that transgenic expression of the T cell costimulator B7-1 on the islets of Langerhans is not sufficient to abolish the in vivo tolerance to islets antigen. Here, we present evidence indicating that the level of major histocompatibility complex (MHC) antigen expressed by islet cells plays a critical role. Mice coexpressing the B7-1 transgene and high levels of the class II MHC antigen I-E on the islets develop an autoimmune destruction of the beta cells of the pancreas. By contrast, expression of the I-E molecule by islets, in the absence of T cell costimulator, leads to specific tolerance of these autoreactive T cells that cannot be reversed by costimulation with B7-1.
T细胞对外周抗原的耐受性被认为主要是由于实质细胞因缺乏T细胞共刺激分子的表达而无法以免疫原性形式呈递抗原所致。然而，我们发现，在胰岛上转基因表达T细胞共刺激分子B7-1不足以消除体内对胰岛抗原的耐受性。在此，我们提供的证据表明，胰岛细胞表达的主要组织相容性复合体（MHC）抗原水平起着关键作用。在胰岛上共表达B7-1转基因和高水平II类MHC抗原I-E的小鼠会发生胰腺β细胞的自身免疫性破坏。相比之下，在没有T细胞共刺激分子的情况下，胰岛表达I-E分子会导致这些自身反应性T细胞产生特异性耐受性，而这种耐受性不能通过用B7-1共刺激来逆转。
