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Publication : Selection of peripheral and intestinal T lymphocytes lacking CD3 zeta.

First Author  Simpson S Year  1995
Journal  Int Immunol Volume  7
Issue  2 Pages  287-93
PubMed ID  7734423 Mgi Jnum  J:112985
Mgi Id  MGI:3664163 Doi  10.1093/intimm/7.2.287
Citation  Simpson S, et al. (1995) Selection of peripheral and intestinal T lymphocytes lacking CD3 zeta. Int Immunol 7(2):287-93
abstractText  The CD3 zeta chain of the TCR plays a pivotal role in the activation of T cell responses toward foreign antigen and in the selection of the T cell repertoire. T lymphocytes from mice deficient in CD3 zeta (CD3 zeta/eta-/- mice) express very few cell surface TCR-CD3 complexes, and these animals have poorly developed thymuses which lack single-positive CD8 and CD4 thymocytes. Nevertheless, a substantial number of single-positive CD4+ and CD8+ T lymphocytes are found in peripheral lymphoid organs of CD3 zeta/eta-/- animals. Using double-mutant mice, generated by breeding CD3 zeta/eta-/- mice with others deficient in the expression of either class I or class II MHC molecules, we demonstrate here that positive selection of peripheral CD4+ and CD8+ T lymphocytes can occur in the absence of CD3 zeta/eta molecules. Analysis of the intestinal intra-epithelial lymphocytes from CD3 zeta/eta-/- mice revealed a novel T cell population expressing high levels of an alternative TCR alpha beta, due to the replacement of CD3 zeta by Fc epsilon RI gamma. Developmentally, these cells also depend on class I MHC expression. In contrast, TCR gamma delta/Fc epsilon RI gamma+ T cells develop independently of MHC class I or class II molecules. These experiments demonstrate that the unique subset of intestinal TCR alpha beta/Fc epsilon RI gamma+ lymphocytes is developmentally dependent on MHC expression. The restricted expression of TCR alpha beta/Fc epsilon RI gamma+ cells in the intestinal mucosa (rather than the thymus or lymph nodes) supports the hypothesis that selection of these T cells occurs extrathymically.
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