CD103 downregulation marks memory-phenotype CD8 T cells and excludes them from the gut (CAM1P.231)

Abstract

Abstract CD103 is a cell surface integrin whose primary role is the retention of lymphocytes in epithelial tissues where its ligand E-cadherin is expressed. CD103 is found on all newly generated CD8 single positive thymocytes but not on CD4 lineage cells. Because of such lineage specific expression, CD103 is currently considered a lineage specific marker whose expression is proposed to be controlled by Runx3, a runt-family transcription factor involved in CD8 lineage specification. Here we report the surprising finding that Runx3 was neither necessary nor sufficient for CD103 expression on CD8 T cells. Notably, we identified a subpopulation of CD8 T cells that had downregulated CD103 expression, despite expressing high levels of Runx3. Upon correlating CD103 expression with activation and memory markers, we found that CD103-negative CD8 T cells corresponded to memory phenotype cells and that homeostatic cytokines signals terminated CD103 expression on CD8 T cells. Importantly, CD103-negative CD8 T cells were found in every lymphoid organ and other peripheral tissues with the exception of the gut. Indeed, all CD8+ IELs were CD103-positive, and adoptive transfer of CD103-negative CD8 T cells resulted in their recovery from the LN but not the intestinal mucosal tissues. Collectively, these results suggest that CD8 memory-phenotype acquisition is accompanied by CD103 downregulation to control their tissue distribution and to exclude them from the gut.