Gangadharan Denise, Lambolez Florence, Attinger Antoine, Wang-Zhu Yiran, Sullivan Barbara A, Cheroutre Hilde
La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, California 92037, USA.
Immunity. 2006 Oct;25(4):631-41. doi: 10.1016/j.immuni.2006.08.018.
The immune system preserves and makes use of autoreactive lymphocytes with specialized functions. Here we showed that one of these populations, CD8alphaalpha(+)TCRalphabeta(+) intestinal intraepithelial lymphocytes (IELs), arose from a unique subset of double-positive thymocytes. This subset of cells was precommitted to preferentially give rise to CD8alphaalpha(+)TCRalphabeta(+) IELs, but they required exposure to self-agonist peptides. The agonist-selected TCRalphabeta(+) thymocytes are CD4 and CD8 double-negative, and their final maturation, including the induction of CD8alphaalpha expression, appeared to occur only after thymus export in the IL-15-rich environment of the gut. These developmental steps, including precommitment of immature thymocytes, TCR-mediated agonist selection, and postthymic differentiation promoted by cytokines, define a unique pathway for the generation of CD8alphaalpha(+)TCRalphabeta(+) IEL.
免疫系统保留并利用具有特殊功能的自身反应性淋巴细胞。在此我们表明,这些细胞群体之一,即CD8αα(+)TCRαβ(+)肠道上皮内淋巴细胞(IEL),源自双阳性胸腺细胞的一个独特亚群。该细胞亚群预先倾向于优先产生CD8αα(+)TCRαβ(+) IEL,但它们需要接触自身激动剂肽。经激动剂选择的TCRαβ(+)胸腺细胞为CD4和CD8双阴性,其最终成熟,包括CD8αα表达的诱导,似乎仅在胸腺输出后于肠道富含IL-15的环境中发生。这些发育步骤,包括未成熟胸腺细胞的预先倾向、TCR介导的激动剂选择以及细胞因子促进的胸腺后分化,定义了产生CD8αα(+)TCRαβ(+) IEL的独特途径。