Origin of regulatory T cells with known specificity for antigen
Origin of regulatory T cells with known specificity for antigen
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DOI：
10.1038/ni816
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发表时间：
2002-08-01
影响因子：
30.5
通讯作者：
von Boehmer, H
中科院分区：
文献类型：
--
作者：
Apostolou, I;Sarukhan, A;von Boehmer, H
T细胞受体激动剂可以诱导调节性T （T- r）细胞的分化。我们在这里报道了免疫球蛋白kappa控制的激动剂在不同细胞类型中的表达与生成的TR细胞的表型相关。我们发现胸腺基质上的异常表达主要产生CD4(+)CD25(+) T-R细胞，在生理条件下，这些细胞可能被异位表达的器官特异性抗原诱导，从而阻止器官特异性自身免疫。非活化的造血细胞表达激动剂抗原，主要产生CD4(+)CD25(-) T-R细胞。这个亚群可以在没有其他T细胞“指导”的情况下从成熟的单特异性T细胞中产生，也可以在没有功能胸腺的情况下产生。CD25（+）和CD25（-）亚群对CD4(+)T细胞增殖反应的抑制是不依赖于白细胞介素10 （IL-10）的，并被IL-2克服。这些数据表明，可以利用不同的途径来干扰不必要的免疫反应。
T cell receptor agonists can induce the differentiation of regulatory T (T-R) cells. We report here that the immunoglobulin kappa-controlled expression of an agonist in different cell types correlated with the phenotype of the generated TR cells. We found that aberrant expression on thymic stroma yielded predominantly CD4(+)CD25(+) T-R cells, which-under physiological conditions-may be induced by ectopically expressed organ-specific antigens and thus prevent organ-specific autoimmunity. Expression of the agonist antigen by nonactivated hematopoietic cells produced mostly CD4(+)CD25(-) T-R cells. This subset can be derived from mature monospecific T cells without "tutoring" by other T cells and can be generated in the absence of a functioning thymus. Suppression of CD4(+)T cell proliferative responses by both CD25(+) and CD25(-) subsets was interleukin 10 (IL-10)-independent and was overcome by IL-2. These data suggest that distinct pathways can be exploited to interfere with unwanted immune responses.