REGULATION OF THE EPITHELIAL CELL-SPECIFIC INTEGRIN, CD103, BY HUMAN CD8+ CYTOLYTIC T LYMPHOCYTES1

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Abstract
The destruction of the graft epithelium by CD8+ cytolytic T lymphocytes (CTL) is an important aspect of organ allograft rejection. Our recent finding in a mouse model that the epithelial cell-specific integrin, CD103, defines a subset of CD8+ CTL potentially sheds new light onto such interactions. The goal of the present study was to assess the relevance of these data to the human system. CD103 expression by human T-cell populations generated in mixed lymphocyte cultures or isolated from transplant nephrectomy specimens was quantitated using multiparameter FACS analyses. CD103 defined a major subset (26-76%) of CD8+ CTL generated in human mixed lymphocyte cultures; cell sorting experiments confirmed that the CD103+ and CD103− subsets both possess allospecific lytic activity. Anti-transforming growth factor (TGF)-β blocked the appearance of the CD103+ CTL subset, and persistent expression of CD103 by CD8+ CTL was dependent on bioactive TGF-β. Isolated CD103+ and CD103− CD8 subsets maintained their phenotypic integrity during in vitro expansion, although optimal CD103 expression on the former was TGF-β dependent. Although CD103+ cells were rare among activated CD8 cells in peripheral lymphoid compartments ( We conclude that CD103 defines a discrete and stable subset of human CD8+ CTL and that CD103 expression by such cells is initiated and maintained by bioactive TGF-β. These data point to the existence of a human effector subset that is uniquely specialized for the destruction of the graft epithelium.