Fatenejad S, Peng S L, Disorbo O, Craft J
Section of Rheumatology, Yale University School of Medicine, New Haven, CT 06520-8031, USA.
J Immunol. 1998 Dec 1;161(11):6427-32.
Lupus-prone mice develop a systemic autoimmune disease that is dependent upon the B cell help provided by autoreactive alphabeta CD4+ T cells. Since autoreactive T cells with high affinity for self peptides are normally deleted in the thymus, their presence in these mice suggests the possibility that intrathymic negative selection may be defective. Here, we directly compared central T cell tolerance in response to a conventional peptide Ag in lupus-prone MRL/MpJ mice with a nonautoimmune strain using an MHC class II-restricted TCR transgene. Our results did not demonstrate any defects after Ag exposure in the induction of intrathymic deletion of immature CD4+ CD8+ thymocytes, in TCR down-regulation, or in the number of apoptotic thymocytes in MRL/MpJ compared with nonautoimmune mice. Furthermore, we found that the lpr mutation had no influence upon the Ag-induced thymic deletion of immature thymocytes. These data support the notion that T cell autoreactivity in MRL/MpJ mice is caused by defects in peripheral control mechanisms.
易患狼疮的小鼠会发展出一种全身性自身免疫疾病，该疾病依赖于自身反应性αβ CD4+ T细胞提供的B细胞辅助。由于对自身肽具有高亲和力的自身反应性T细胞通常在胸腺中被清除，它们在这些小鼠中的存在表明胸腺内阴性选择可能存在缺陷。在此，我们使用MHC II类限制性TCR转基因，直接比较了易患狼疮的MRL/MpJ小鼠与非自身免疫品系对传统肽抗原的中枢T细胞耐受性。与非自身免疫小鼠相比，我们的结果并未显示在抗原暴露后，MRL/MpJ小鼠在诱导未成熟CD4+ CD8+胸腺细胞的胸腺内缺失、TCR下调或凋亡胸腺细胞数量方面存在任何缺陷。此外，我们发现lpr突变对未成熟胸腺细胞的抗原诱导胸腺缺失没有影响。这些数据支持了MRL/MpJ小鼠中的T细胞自身反应性是由外周控制机制缺陷引起的这一观点。
