Abstract
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.
Original language | English |
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Journal | EMBO Journal |
Volume | 43 |
Issue number | 14 |
Pages (from-to) | 2878-2907 |
ISSN | 0261-4189 |
DOIs | |
Publication status | Published - 2024 |
Keywords
- Cancer
- Differentiation
- IL-27
- Innate
- γδ T Cells