TLR Activation Excludes Circulating Naive CD8+ T Cells from Gut-Associated Lymphoid Organs in Mice

The trafficking of effector T cells is tightly regulated by the expression of site-specific sets of homing molecules. In contrast, naive T cells are generally assumed to express a uniform pattern of homing molecules and to follow a random distribution within the blood and secondary lymphoid organs. In this study, we demonstrate that systemic infection fundamentally modifies the trafficking of circulating naive CD8 + T cells. We show that on naive CD8 + T cells, the constitutive expression of the integrin α 4 β 7 that effects their entry into GALT is downregulated following infection of mice with Salmonella typhimurium . We further show that this downregulation is dependent on TLR signaling, and that the TLR-activated naive CD8 + T cells are blocked from entering GALT. This contrasts strongly with Ag-experienced effector T cells, for which TLR costimulation in the GALT potently upregulates α 4 β 7 and enhances trafficking to intestinal tissues. Thus, TLR activation leads to opposite effects on migration of naive and effector CD8 + T cells. Our data identify a mechanism that excludes noncognate CD8 + T cells from selected immune compartments during TLR-induced systemic inflammation.