Failure of T cell receptor Vβ negative selection in murine intestinal intra-epithelial lymphocytes

Abstract

The intestinal intra-epithelial lymphocytes (IEL) are divided into several subsets on the basis of expression of T cell receptor (TCR) αβ and γδ 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_β segments of T cells in the IEL in BALB/c (H-2^d, MIs-1^b2^a) or AKR/J (H-2^k, MIs-1^a2^b) mice. Among freshly isolated IEL, an appreciable number of T cells bearing V_β3 or V_β11, which recognize MIs-2^a- or MHC IE-encoded molecules respectively, were detected in BALB/c mice. Similarly, in AKR/J mice, IEL contained appreciable levels of V_β6-bearing T cells. V_β3- or V_β11-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_β3- and V_β11-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 TCRαβ-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.