Although T cells bearing yv T-cell receptors have long been known to be present in the epithelial lining of many organs, their specificity and function remain elusive. In the present study, we examined the intestinal epithelia of T-cell-receptor mutant mice, which were deficient in either yS T cells or ca3 T cells, and of normal littermates. The absence of yS T cells was associated with a reduction in epithelial cell turnover and a downregulation of the expression of major histocompatibility complex class II molecules. No such effects were observed in a38 T-cell-deficient mice. These findings indicate that intraepithelial yeS T cells regulate the generation and differentiation of intestinal epithelial cells.

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We have compared the cytolytic activities and the cellular compositions of the inal lntraeplthellal lymphocyte (i-IEL) populations in three different combinations of conventional (CV) and germ-free (GF) mice. Cytolytic activity of i-EELs exps yS T-l antigen receptors (TCRs) b strain dependent in CV mice (high vs. low), and this straindependent variability b unaltered in the GF condition. Although absolute numbers of yv i-IELs are sightly decrased, the composition of CD8aa+ and CD4-CD8-subsets and the usage of TCR r and 8-chain variable gene segments by yS i-EELs remain the same in GF mice. By contrast, cytolytic activity of ar TCR-expressing i-JELs is uniformly high in CV mice but attenuated sharply in the GF condltion. A conspicuous decrease in the total numbers of afl i-IELs is also noted, and CD8rP+ and CD4+CD8+ subsets are reduced, whereas the CD8aa+ subset is expanded in GF mice. These rults indicate that microbial deprivation preferentially influences the a,B i-EEL population to decrease and become noncytolytic but has little effect on the pd size or characteristics of yS i-EELs. Consequently, cytolytic activity of feshly isolated i-KELs from GF mce b determined by T cellsexp ng y8TCRs and is found to be strin dependent.