T cell receptor signaling strength establishes the chemotactic properties of effector CD8(+) T cells that control tissue-residency

Tissue-resident memory (T(RM)) CD8(+) T cells are largely derived from recently activated effector T cells, but the mechanisms that control the extent of T(RM) differentiation within tissue microenvironments remain unresolved. Here, using an IFNγ-YFP reporter system to identify CD8(+) T cells executing antigen-dependent effector functions, we define the transcriptional consequences and functional mechanisms controlled by TCR-signaling strength that occur within the skin during viral infection to promote T(RM) differentiation. TCR-signaling both enhances CXCR6-mediated migration and suppresses migration toward sphingosine-1-phosphate, indicating the programming of a ‘chemotactic switch’ following secondary antigen encounter within non-lymphoid tissues. Blimp1 was identified as the critical target of TCR re-stimulation that is necessary to establish this chemotactic switch and for T(RM) differentiation to efficiently occur. Collectively, our findings show that access to antigen presentation and strength of TCR-signaling required for Blimp1 expression establishes the chemotactic properties of effector CD8(+) T cells to promote residency within non-lymphoid tissues.