CD4+ T cell help impairs CD8+ T cell deletion induced by cross-presentation of self-antigens and favors autoimmunity.
CD4+ T cell help impairs CD8+ T cell deletion induced by cross-presentation of self-antigens and favors autoimmunity.
复制标题
DOI：
10.1084/jem.186.12.2057
复制
发表时间：
1997-12-15
期刊：
影响因子：
--
通讯作者：
Miller JF
中科院分区：
文献类型：
--
作者：
Kurts C;Carbone FR;Barnden M;Blanas E;Allison J;Heath WR;Miller JF
在胸腺外组织如胰腺中表达的自身抗原可被转运至引流淋巴结，并通过骨髓来源的抗原呈递细胞以I类限制性方式呈递。这种自身抗原的交叉呈递通过缺失导致CD8+ T细胞耐受性诱导。在这份报告中，我们研究了CD4+ T细胞帮助对这一过程的影响。当将少量自身反应性OVA特异性CD8+ T细胞过继转移到在胰腺β细胞中表达卵清蛋白的小鼠中时，其不能引起糖尿病。然而，共同注射OVA特异性CD4+辅助性T细胞导致大部分小鼠（68%）患糖尿病，这表明提供帮助有利于诱导自身免疫。对CD8+ T细胞命运的分析表明，CD4+ T细胞帮助损害了它们的缺失。这些数据表明，控制这种帮助对于维持交叉呈递诱导的CD8+ T细胞耐受性至关重要。
Self-antigens expressed in extrathymic tissues such as the pancreas can be transported to draining lymph nodes and presented in a class I–restricted manner by bone marrow-derived antigen-presenting cells. Such cross-presentation of self-antigens leads to CD8+ T cell tolerance induction via deletion. In this report, we investigate the influence of CD4+ T cell help on this process. Small numbers of autoreactive OVA-specific CD8+ T cells were unable to cause diabetes when adoptively transferred into mice expressing ovalbumin in the pancreatic β cells. Coinjection of OVA-specific CD4+ helper T cells, however, led to diabetes in a large proportion of mice (68%), suggesting that provision of help favored induction of autoimmunity. Analysis of the fate of CD8+ T cells indicated that CD4+ T cell help impaired their deletion. These data indicate that control of such help is critical for the maintenance of CD8+ T cell tolerance induced by cross-presentation.