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IL-27 maintains cytotoxic Ly6C+ γδ T cells that arise from immature precursors.
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.
Afiliación
  • Wiesheu R; School of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
  • Edwards SC; Cancer Research UK Scotland Institute, Glasgow, UK.
  • Hedley A; School of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
  • Hall H; Cancer Research UK Scotland Institute, Glasgow, UK.
  • Tosolini M; Cancer Research UK Scotland Institute, Glasgow, UK.
  • Fares da Silva MGF; Cancer Research UK Scotland Institute, Glasgow, UK.
  • Sumaria N; Cancer Research Centre of Toulouse, University of Toulouse, Toulouse, France.
  • Castenmiller SM; Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
  • Wardak L; Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
  • Optaczy Y; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
  • Lynn A; Department Of Hematopoiesis, Sanquin Research, Amsterdam, The Netherlands.
  • Hill DG; Oncode Institute, Utrecht, The Netherlands.
  • Hayes AJ; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
  • Hay J; Department Of Hematopoiesis, Sanquin Research, Amsterdam, The Netherlands.
  • Kilbey A; Oncode Institute, Utrecht, The Netherlands.
  • Shaw R; Cancer Research UK Scotland Institute, Glasgow, UK.
  • Whyte D; School of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
  • Walsh PJ; Cancer Research UK Scotland Institute, Glasgow, UK.
  • Michie AM; School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
  • Graham GJ; School of Infection & Immunity, University of Glasgow, Glasgow, UK.
  • Manoharan A; School of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
  • Halsey C; School of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
  • Blyth K; Cancer Research UK Scotland Institute, Glasgow, UK.
  • Wolkers MC; Cancer Research UK Scotland Institute, Glasgow, UK.
  • Miller C; Cancer Research UK Scotland Institute, Glasgow, UK.
  • Pennington DJ; Cancer Research UK Scotland Institute, Glasgow, UK.
  • Jones GW; School of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
  • Fournie JJ; School of Infection & Immunity, University of Glasgow, Glasgow, UK.
  • Bekiaris V; School of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
  • Coffelt SB; School of Cancer Sciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
EMBO J ; 43(14): 2878-2907, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38816652
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 αß-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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos Ly / Receptores de Antígenos de Linfocitos T gamma-delta / Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos Ly / Receptores de Antígenos de Linfocitos T gamma-delta / Miembro 7 de la Superfamilia de Receptores de Factores de Necrosis Tumoral Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido