HETEROGENEITY AND BIASED T-CELL RECEPTOR ALPHA/BETA REPERTOIRE OF MUCOSAL CD8+ CELLS FROM MURINE LARGE-INTESTINE - IMPLICATIONS FOR FUNCTIONAL-STATE

Up to 90% of CD8(+) intraepithelial lymphocytes (IEL) of the murine large intestine (LI) belong to the alpha/beta T cell lineage and consist of two subsets. One subset expresses both alpha and beta subunits of the CD8 coreceptor, and is uniformly Thy1(+), CD5(+), B220(-), CD2(+), CD28(+). The CD8 alpha(+)beta(+) LI-IEL exclude self-reacting V-beta structures, and readily proliferate in vivo in response to T cell receptor-mediated stimuli. The CD8 alpha(+)beta(-) subset of TCR-alpha/beta(+) LI-IEL is Thy1(-/+) CD5(-), B220(+), CD2(+/-), and CD28(-). It contains cells with potentially self-reacting V-beta s and is responsive in vivo to high doses of anti-TCR-alpha/beta monoclonal antibody (mAb), but not to bacterial superantigens. Both subsets are abundant in LI-IEL of old nude mice, and CD8 alpha(+)beta(+) LI-IEL in nude mice undergo the same V-beta deletions as in euthymic mice of the same background. Both subsets express the intestinal T cell-specific integrin alpha(M290)beta 7, known to be a homing receptor for IEL. Unusually high proportions of CD69(+) cells within both subsets indicate chronic activation. The proportions of CD69(+) and alpha(M290)beta 7(+) cells within the CD8 alpha(+)beta(+) subset increase with age, probably due to constant antigenic challenge. We propose that CD8 alpha(+)beta(+) and CD8 alpha(+)beta(-) subsets of LI-IEL permanently reside in LI and represent a lineage different from spleen and lymph node CD8(+) T cells. The CD8 alpha(+)beta(+) undergoes negative selection, and is responsive to TCR-mediated stimuli. The CD8 alpha(+)beta(-) subset of LI-IEL is a subject of distinct selection mechanisms, and has low responsiveness to TCR-mediated stimuli.