FAILURE OF T-CELL RECEPTOR V-BETA NEGATIVE SELECTION IN MURINE INTESTINAL INTRAEPITHELIAL LYMPHOCYTES

The intestinal intra-epithelial lymphocytes (IEL) are divided into several subsets on the basis of expression of T cell receptor (TCR) alpha-beta and gamma-delta, intensity of Thy-1 expression and expression of Lyt-3 chain. To investigate the differentiation pathway of the IEL, we examined the repertoire of V-beta segments of T cells in the IEL in BALB/c (H-2d, MIs-lb2a) or AKR/J (H-2k, MIS-1a2b) mice. Among freshly isolated IEL, an appreciable number of T cells bearing V-beta-3 or V-beta-11, which recognize MIs-2a- or MHC IE-encoded molecules respectively, were detected in BALB/c mice. Similarly, in AKR/J mice, IEL contained appreciable levels of V-beta-6-bearing T cells. V-beta-3- or V-beta-11-bearing T cells in the IEL in BALB/c mice increased to a significant level when incubated with staphylococcal enterotoxin A which specifically stimulates V-beta-3- and V-beta-11-bearing T cells. Most of IEL without clonal deletion expressed Lyt-2 but not Lyt-3 antigens. Such T cells were hardly detected in other organs, including liver. Our results indicate that TCR-alpha-beta-bearing intestinal IEL that have not undergone negative selection may have differentiated outside the thymus, presumably at a local site of the intestine and can respond normally to the signal via their TCR.