Article Dans Une Revue EMBO Journal Année : 2024

IL-27 maintains cytotoxic Ly6C+ γδ T cells that arise from immature precursors

Ann Hedley
Holly Hall
Gareth W Jones

Résumé

In mice, γδ-T lymphocytes that express the co-stimulatory molecule, CD27, are committed to the IFNγ-producing lineage during thymic development. In the periphery, these cells play a critical role in host defense and anti-tumor immunity. Unlike αβ-T cells that rely on MHC-presented peptides to drive their terminal differentiation, it is unclear whether MHC-unrestricted γδ-T cells undergo further functional maturation after exiting the thymus. Here, we provide evidence of phenotypic and functional diversity within peripheral IFNγ-producing γδ T cells. We found that CD27 + Ly6C -cells convert into CD27 + Ly6C + cells, and these CD27 + Ly6C + cells control cancer progression in mice, while the CD27 + Ly6C - cells cannot. The gene signatures of these two subsets were highly analogous to human immature and mature γδ-T cells, indicative of conservation across species. We show that IL-27 supports the cytotoxic phenotype and function of mouse CD27 + Ly6C + cells and human Vδ2 + cells, while IL-27 is dispensable for mouse CD27 + Ly6C -cell and human Vδ1 + cell functions. These data reveal increased complexity within IFNγ-producing γδ-T cells, comprising immature and terminally differentiated subsets, that offer new insights into unconventional T-cell biology.

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inserm-04773446 , version 1 (08-11-2024)

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Robert Wiesheu, Sarah C Edwards, Ann Hedley, Holly Hall, Marie Tosolini, et al.. IL-27 maintains cytotoxic Ly6C+ γδ T cells that arise from immature precursors. EMBO Journal, 2024, 43 (14), pp.2878 - 2907. ⟨10.1038/s44318-024-00133-1⟩. ⟨inserm-04773446⟩
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