T cell receptor signaling strength establishes the chemotactic properties of effector CD8+ T cells that control tissue-residency
Year: 2023
Type: article
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 TRMdifferentiation 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 TRMdifferentiation. 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 TRMdifferentiation 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.
Source: Nature Communications
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,290
OpenAlex ID: W4383105643