Regulation of the epithelial cell-specific integrin, CD103, by human CD8+ cytolytic T lymphocytes

Background. 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, Methods. CD103 expression by human T-cell populations generated in mixed lymphocyte cultures or isolated from transplant nephrectomy specimens was quantitated using multiparameter FAGS analyses. Results, 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)-beta blocked the appearance of the CD103(+) CTL subset, and persistent expression of CD103 by CD8(+) CTL was dependent on bioactive TGF-beta, Isolated CD103(+) and CD103(-) CD8 subsets maintained their phenotypic integrity during in vitro expansion, although optimal CD103 expression on the former was TGF-beta dependent. Although CD103(+) cells were rare among activated CD8 cells in peripheral lymphoid compartments (<10%), analyses of transplant nephrectomy specimens revealed that a major subset (21-61%) of CD8 memory/effector cells that infiltrate rejecting renal allografts express high levels of CD103, Conclusions, 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 TGP-beta, These data point to the existence of a human effector subset that is uniquely specialized for the destruction of the graft epithelium.