Phenotypic and functional assessment of intraepithelial lymphocytes bearing a ‘forbidden’ αβ TCR

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Abstract
Differences in the surface antigen phenotype, such as the expression CD8 as an αα 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’ Vβ6 TCR in Mls-1a mice and to γδ TCR. The results indicate that CD5 expression was absent on the majority of TCR γδ IEL (96.9%) and on a significant proportion of TCR αβ IEL (25.0%). Virtually all IEL In DBA/2 (Mls-1a) mice that expressed the ‘autospecific’ Vβ6 TCR were CD5−, and this correlated with the expression of CD8 αα. 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 Vβ6, In Mls-1a mice, were not responsive to TCR-mediated activation. Similarly, TCR γδ IEL were not responsive to stimulation by anti-TCR γδ antibodies. The addition of exogenous IL-2, however, reconstituted the prollferative response of both TCR γδ IEL and the TCR Vβ6 expressing IEL. We conclude that the lack of CD5 defines a unique subset of intraepithelial T cells expressing either TCR γδ or αβ that Include potentially autoreactive cells that remain anergic in the absence of IL-2.

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