Poussier P, Edouard P, Lee C, Binnie M, Julius M
Department of Medicine, McGill University, Montreal, Quebec, Canada.
J Exp Med. 1992 Jul 1;176(1):187-99. doi: 10.1084/jem.176.1.187.
We demonstrate that mouse intestinal intraepithelial lymphocytes (IEL) can be divided into subsets based on the differential expression of functional T cell receptor alpha/beta (TCR-alpha/beta) signaling complexes. Two subsets, CD4+ 8 alpha + beta - and CD8 alpha + beta -, are refractory to stimulation with anti-TCR-alpha/beta and contain high frequencies of potentially self-reactive cells. In contrast, the CD4+ and CD8 alpha + beta + IEL subsets are responsive to anti-TCR-alpha/beta and depleted of potentially self-reactive cells. The analysis of fetal liver radiation chimeras using adult thymectomized recipients demonstrates that the four TCR-alpha/beta + IEL subsets are generated in normal numbers in the absence of the thymus. Moreover, expression of the major histocompatibility complex class II-encoded I-E molecule and Mls1a in the gut of the athymic host results in the negative selection of potentially self-reactive T cells expressing V beta 11 and V beta 6, respectively, from those IEL subsets that express functional TCR-alpha/beta signaling complexes. Neither the spleen nor the Peyer's patches of athymic recipients contain T cells of donor origin. In contrast, normal numbers of phenotypically and functionally mature CD4+ and CD8 alpha + beta + T cells of donor origin are found in the lamina propria of chimeric animals. The phenotypic analysis of lymphocytes obtained from Ly5 congenic parabionts reveals that peripheral T cells migrate rapidly to the Peyer's patches and lamina propria, but not to the intestinal epithelium. Taken together, these results demonstrate that the intestinal epithelium is a thymus-independent site of T lymphopoiesis, where selection of the T cell repertoire involves the deletion of potentially self-reactive cells in situ. Moreover, the appearance of donor-derived, phenotypically mature T cells, exclusively in the lamina propria of athymic radiation chimeras, suggests that mature IEL expressing functional TCR-alpha/beta migrate to this site.
我们证明，小鼠肠道上皮内淋巴细胞（IEL）可根据功能性T细胞受体α/β（TCR-α/β）信号复合物的差异表达分为不同亚群。两个亚群，CD4 + 8α + β - 和CD8α + β - ，对抗-TCR-α/β刺激无反应，并且含有高频率的潜在自身反应性细胞。相比之下，CD4 +和CD8α + β + IEL亚群对抗-TCR-α/β有反应，并且潜在自身反应性细胞减少。使用成年去胸腺受体对胎肝辐射嵌合体进行的分析表明，在没有胸腺的情况下，四个TCR-α/β + IEL亚群以正常数量产生。此外，无胸腺宿主肠道中主要组织相容性复合体II类编码的I-E分子和Mls1a的表达分别导致从表达功能性TCR-α/β信号复合物的那些IEL亚群中阴性选择表达Vβ11和Vβ6的潜在自身反应性T细胞。无胸腺受体的脾脏和派尔集合淋巴结均不含有供体来源的T细胞。相反，在嵌合动物的固有层中发现了正常数量的表型和功能成熟的供体来源的CD4 +和CD8α + β + T细胞。从Ly5同基因联体动物获得的淋巴细胞的表型分析表明，外周T细胞迅速迁移到派尔集合淋巴结和固有层，但不迁移到肠道上皮。综上所述，这些结果表明肠道上皮是T淋巴细胞生成的胸腺非依赖部位，其中T细胞库的选择涉及原位删除潜在的自身反应性细胞。此外，仅在无胸腺辐射嵌合体的固有层中出现供体来源的、表型成熟的T细胞，表明表达功能性TCR-α/β的成熟IEL迁移到该部位。
