Heterogeneity and biased T cell receptor α/β repertoire of mucosal CD8+ cells from murine large intestine: Implications for functional state

Abstract

Up to 90% of CD8+ intraepithelial lymphocytes (IEL) of the murine large intestine (LI) belong to the α/β T cell lineage and consist of two subsets. One subset expresses both α and β subunits of the CD8 coreceptor, and is uniformly Thy1+, CD5+, B220-, CD2+, CD28+. The CD8α+β+ LI-IEL exclude self-reacting V(β) structures, and readily proliferate in vivo in response to T cell receptor-mediated stimuli. The CD8α+β- subset of TCR- α/β+ LI-IEL is Thy1(-/+), CD5-, B220+, CD2(+/-), and CD28-. It contains cells with potentially self-reacting V(β)s and is responsive in vivo to high doses of anti-TCR-α/β monoclonal antibody (mAb), but not to bacterial superantigens. Both subsets are abundant in LI-IEL of old nude mice, and CD8α+β+ LI-IEL in nude mice undergo the same V(β) deletions as in euthymic mice of the same background. Both subsets express the intestinal T cell-specific integrin α(M290)β7, 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 α(M290)β7+ cells within the CD8α+β+ subset increase with age, probably due to constant antigenic challenge. We propose that CD8α+β+ and CD8α+β- subsets of LI-IEL permanently reside in LI and represent a lineage different from spleen and lymph node CD8+ T cells. The CD8α+β+ undergoes negative selection, and is responsive to TCR-mediated stimuli. The CD8α+β- subset of LI-IEL is a subject of distinct selection mechanisms, and has low responsiveness to TCR- mediated stimuli.