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Thymus-independent development and negative selection of T cells expressing T cell receptor alpha/beta in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes


Thymus-independent development and negative selection of T cells expressing T cell receptor alpha/beta in the intestinal epithelium: evidence for distinct circulation patterns of gut- and thymus-derived T lymphocytes



Journal of Experimental Medicine 176(1): 187-199



ISSN/ISBN: 0022-1007

PMID: 1535367

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 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.

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Accession: 007951380

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