Cozzo Cristina, Larkin Joseph, Caton Andrew J
The Wistar Institute, Philadelphia, PA 19104, USA.
J Immunol. 2003 Dec 1;171(11):5678-82. doi: 10.4049/jimmunol.171.11.5678.
CD4(+)CD25(+) regulatory T cell selection is initiated by high-specificity interactions with self-peptides in the thymus, although how these cells respond to cytokine-derived signals and to re-exposure to self-peptide:MHC complexes in the periphery is not well understood. We have used a transgenic mouse system, in which the peptide that induces thymic selection of a clonal population of CD4(+)CD25(+) regulatory T cells is known, to show that CD4(+)CD25(+) T cells proliferate in response to their selecting self-peptide in vivo. Moreover, they do not proliferate in response to lymphopenia in the absence of the selecting self-peptide, reflecting a low level of expression of the high affinity receptor for IL-7 (CD127) relative to conventional CD4(+) T cells. That their selecting self-peptide is both required for and promotes the peripheral expansion of CD4(+)CD25(+) regulatory T cells may direct their accumulation in sites where the self-peptide is expressed.
CD4(+)CD25(+)调节性T细胞的选择是由其在胸腺中与自身肽的高特异性相互作用启动的，尽管这些细胞如何对外周细胞因子衍生的信号以及再次暴露于自身肽：MHC复合物作出反应尚不清楚。我们使用了一种转基因小鼠系统，其中诱导CD4(+)CD25(+)调节性T细胞克隆群体胸腺选择的肽是已知的，以表明CD4(+)CD25(+)T细胞在体内对其选择的自身肽作出反应而增殖。此外，在没有选择的自身肽的情况下，它们不会因淋巴细胞减少而增殖，这反映出相对于传统CD4(+)T细胞，它们对IL-7（CD127）的高亲和力受体表达水平较低。它们选择的自身肽对于CD4(+)CD25(+)调节性T细胞的外周扩增既是必需的又是促进性的，这可能指导它们在自身肽表达部位的积累。
