The Epithelial Cell-Specific Integrin, CD103 (α^E Integrin), Defines a Novel Subset of Alloreactive CD8⁺CTL

The interaction of CD8⁺CTL with epithelial layers is an important but poorly defined aspect of organ allograft rejection. We herein report that CD103 (formerly α^E integrin), a known receptor for the epithelial cell-specific ligand E-cadherin, is expressed by a major subset of CD8⁺CTL elicited in response to allogeneic renal epithelial cells (REC). In contrast, CD103 was expressed poorly on CD8⁺CTL generated in the conventional manner by stimulation with allogeneic leukocytes, although expression could be dramatically up-regulated by supplementing cultures with REC or exogenous TGF-β₁. That TGF-β controls the expression of CD103 on CD8⁺CTL was further supported by the capacity of anti-TGF-β mAb to block the generation of such cells in anti-REC cultures. Clonal analyses of anti-REC cultures revealed that individual CD8⁺CTL clones were discretely CD103⁺ or CD103^-, and maintained their respective phenotypes independently of the cell type used for clonal restimulation. In a mouse model of graft-vs-host disease, 16.4 ± 2.7% of CD8 cells that infiltrated host kidneys were CD103⁺ (n = 4). CD8 kidney-infiltrating lymphocytes were predominantly of donor origin and displayed an activated/memory phenotype (CD62L^-, CD44^high), consistent with expression of CD103 on a CD8 effector subset elicited in vivo following allogeneic transplantation. Taken together, the present data demonstrate that CD103 identifies a novel CD8 effector subset and, moreover, that such cells may comprise a significant component of the response to allogeneic tissues. The potential for CD103⁺CTL as an important effector mechanism in organ allograft rejection, and more generally, as a mechanistic basis for tissue-specific immune phenomena, is discussed.