Department of Immunology, University of Washington, Seattle, WA 98195, USA.
J Immunol. 2010 Jun 1;184(11):5964-8. doi: 10.4049/jimmunol.1000876. Epub 2010 Apr 30.
Mature CD4(+)Vbeta5(+) T cells that recognize a peripherally expressed endogenous superantigen are tolerized either by deletion or TCR revision. In Vbeta5 transgenic mice, this latter tolerance pathway results in the appearance of CD4(+)Vbeta5(-)TCRbeta(+) T cells, coinciding with Rag1, Rag2, and TdT expression and the accumulation of V(beta)-DJ(beta) recombination intermediates in peripheral CD4(+) T cells. Because postthymic RAG-dependent TCR rearrangement has remained controversial, we sought to definitively determine whether TCR revision is an extrathymic process that occurs in mature peripheral T cells. We show in this study that Rag deletion in post-positive selection T cells in Vbeta5 transgenic mice blocks TCR revision in vivo and that mature peripheral T cells sorted to remove cells bearing endogenous TCRbeta-chains can express newly generated TCRbeta molecules in adoptive hosts. These findings unambiguously demonstrate postthymic, RAG-dependent TCR rearrangement and define TCR revision as a tolerance pathway that targets mature peripheral CD4(+) T cells.
成熟的 CD4(+)Vbeta5(+)T 细胞可通过删除或 TCR 修正来耐受识别外周表达的内源性超抗原。在 Vbeta5 转基因小鼠中，这种后者的耐受途径导致 CD4(+)Vbeta5(-)TCRbeta(+)T 细胞的出现，与 Rag1、Rag2 和 TdT 表达以及外周 CD4(+)T 细胞中 V(beta)-DJ(beta)重组中间产物的积累相吻合。因为胸腺后 RAG 依赖性 TCR 重排仍然存在争议，我们试图明确确定 TCR 修正是否是发生在成熟外周 T 细胞中的胸腺外过程。我们在这项研究中表明，在 Vbeta5 转基因小鼠中，阳性选择后 T 细胞中的 Rag 删除阻断了体内的 TCR 修正，并且成熟的外周 T 细胞分选以去除携带内源性 TCRbeta 链的细胞，可以在过继宿主中表达新生成的 TCRbeta 分子。这些发现明确证明了胸腺后、RAG 依赖性 TCR 重排，并将 TCR 修正定义为一种针对成熟外周 CD4(+)T 细胞的耐受途径。
