Using an IFNγ-YFP reporter system, Abdelbary et al. showed that epicutaneous VacV infection induced some skin-infiltrating effector CD8+ T cells (TEFF), but not circulating memory T cell precursors to express IFNγ in the presence of antigen. Levels of IFNγ and induction of tissue-resident CD8+ T cell (TRM) differentiation depended on TCR signal strength and expression of the transcriptional repressor Blimp1. Blimp1 was upregulated in TEFF re-exposed to antigen in the periphery, and regulated chemotaxis. Low-affinity TCR agonism bolstered CXCR6-mediated tissue retention, but strong agonism also hindered the complementary pathway of S1P-mediated TEFF egress.
Contributed by Paula Hochman
ABSTRACT: Tissue-resident memory (TRM) CD8+ T cells are largely derived from recently activated effector T cells, but the mechanisms that control the extent of TRM 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 TRM 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 TRM 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.
Author Info: (1) Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA. (2) Department of Molecular Microbiology and Immunology, Oregon Heal
Author Info: (1) Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA. (2) Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA. (3) Cellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. (4) Cellular Biology Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. (5) Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR, USA. nolz@ohsu.edu. Department of Cell, Developmental and Cancer Biology, Oregon Health & Science University, Portland, OR, USA. nolz@ohsu.edu. Department of Dermatology, Oregon Health & Science University, Portland, OR, USA. nolz@ohsu.edu.
