The Wistar Institute, Philadelphia, PA 19104, USA.
Eur J Immunol. 2009 Dec;39(12):3301-6. doi: 10.1002/eji.200939709.
Autoreactive CD4+ T cells can undergo deletion and/or become CD25+Foxp3+ Treg as they develop intrathymically, but how these alternative developmental fates are specified based on interactions with self-peptide(s) is not understood. We show here that thymocytes expressing an autoreactive TCR can be subjected to varying degrees of deletion that correlate with the amount of self-peptide. Strikingly, among thymocytes that evade deletion, similar proportions acquire Foxp3 expression. These findings provide evidence that Foxp3+ Treg can develop among members of a cohort of autoreactive thymocytes that have evaded deletion by a self-peptide, and that deletion and Treg formation can act together to bias the Treg repertoire toward low-abundance self-peptide(s).
自身反应性 CD4+ T 细胞在胸腺内发育时可发生删除和/或成为 CD25+Foxp3+ Treg，但尚不清楚这些替代发育命运是如何基于与自身肽的相互作用来指定的。我们在这里表明，表达自身反应性 TCR 的胸腺细胞可受到与自身肽量相关的不同程度的删除。引人注目的是，在逃避删除的胸腺细胞中，类似比例的细胞获得 Foxp3 表达。这些发现提供了证据表明，Foxp3+ Treg 可以在一群逃避自身肽删除的自身反应性胸腺细胞中发育，并且删除和 Treg 形成可以共同作用，使 Treg 库偏向于低丰度自身肽。
