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

Authors :
Mahmoud Abdelbary
Samuel J. Hobbs
James S. Gibbs
Jonathan W. Yewdell
Jeffrey C. Nolz
Source :
Nature Communications, Vol 14, Iss 1, Pp 1-14 (2023)
Publication Year :
2023
Publisher :
Nature Portfolio, 2023.

Abstract

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.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723 and 48162957
Volume :
14
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.98659d4192e840ac935c48162957b947
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-023-39592-1