PHENOTYPIC AND FUNCTIONAL ASSESSMENT OF INTRAEPITHELIAL LYMPHOCYTES BEARING A FORBIDDEN ALPHA-BETA TCR

Differences in the surface antigen phenotype, such as the expression CD8 as an alpha alpha homodimer or the lack of Thy-1, on intestinal intraepithelial lymphocytes (IEL) are related, in part, to alternative differentiation pathways. The relationship of IEL lacking the pan-T cell marker CD5 to these IEL, their TCR repertoire and function has not been examined directly. We explored the TCR repertoire and function of the CD5(-) IEL subset in relation to the expression of the 'autospecific' V(beta)6 TCR in Mls-1(a) mice and to gamma delta TCR. The results indicate that CD5 expression was absent on the majority of TCR gamma delta IEL (96.9%) and on a significant proportion of TCR alpha beta IEL (25.0%). Virtually all IEL in DBA/2 (Mls-1(a)) mice that expressed the 'autospecific' V(beta)6 TCR were CD5(-), and this correlated with the expression of CD8 alpha alpha. To assess the functional capacity of this subset of IEL, we examined proliferation and IL-2 production in response to TCR activation. Although CD5(-) IEL proliferated in response to anti-CD3, IEL bearing TCR V(beta)6, in Mis-1(a) a mice, were not responsive to TCR-mediated activation. Similarly, TCR gamma delta IEL were not responsive to stimulation by anti-TCR gamma delta antibodies. The addition of exogenous IL-2, however, reconstituted the proliferative response of both TCR gamma delta IEL and the TCR V(beta)6 expressing IEL. We conclude that the lack of CD5 defines a unique subset of intraepithelial T cells expressing either TCR gamma delta or alpha beta that include potentially autoreactive cells that remain anergic in the absence of IL-2.