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

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...

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Published inThe EMBO journal Vol. 43; no. 14; pp. 2878 - 2907
Main Authors Wiesheu, Robert, Edwards, Sarah C, Hedley, Ann, Hall, Holly, Tosolini, Marie, Fares da Silva, Marcelo Gregorio Filho, Sumaria, Nital, Castenmiller, Suzanne M, Wardak, Leyma, Optaczy, Yasmin, Lynn, Amy, Hill, David G, Hayes, Alan J, Hay, Jodie, Kilbey, Anna, Shaw, Robin, Whyte, Declan, Walsh, Peter J, Michie, Alison M, Graham, Gerard J, Manoharan, Anand, Halsey, Christina, Blyth, Karen, Wolkers, Monika C, Miller, Crispin, Pennington, Daniel J, Jones, Gareth W, Fournie, Jean-Jacques, Bekiaris, Vasileios, Coffelt, Seth B
Format Journal Article
LanguageEnglish
Published EMBO Press 30.05.2024
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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.
AbstractList 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.
Author Jones, Gareth W
Pennington, Daniel J
Hedley, Ann
Wolkers, Monika C
Whyte, Declan
Optaczy, Yasmin
Halsey, Christina
Fares da Silva, Marcelo Gregorio Filho
Tosolini, Marie
Michie, Alison M
Hall, Holly
Castenmiller, Suzanne M
Walsh, Peter J
Fournie, Jean-Jacques
Sumaria, Nital
Bekiaris, Vasileios
Wardak, Leyma
Wiesheu, Robert
Manoharan, Anand
Lynn, Amy
Shaw, Robin
Miller, Crispin
Hill, David G
Coffelt, Seth B
Graham, Gerard J
Edwards, Sarah C
Blyth, Karen
Hayes, Alan J
Kilbey, Anna
Hay, Jodie
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Keywords γδ T Cells
Immunology
Innate Subject Categories Cancer
IL-27
Differentiation
Cancer
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Snippet In mice, γδ-T lymphocytes that express the co-stimulatory molecule, CD27, are committed to the IFNγ-producing lineage during thymic development. In the...
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Title IL-27 maintains cytotoxic Ly6C+ γδ T cells that arise from immature precursors
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