γδ T cells provide an early source of interferon γ in tumor immunity

Yunfei Gao, Wancai Yang, Meng Pan, Eileen Scully, Michael Girardi, Leonard H. Augenlicht, Joe Craft, Zhinan Yin

Research output: Contribution to journalArticle

249 Scopus citations

Abstract

Interferon (IFN)-γ is necessary for tumor immunity, however, its initial cellular source is unknown. Because γδ T cells primarily produce this cytokine upon activation, we hypothesized that they would provide an important early source of IFN-γ in tumor immunosurveillance. To address this hypothesis, we first demonstrated that γδ T cell-deficient mice had a significantly higher incidence of tumor development after challenge with a chemical carcinogen methylcholanthrene (MCA) or inoculation with the melanoma cell line B16. In wild-type mice, γδ T cells were recruited to the site of tumor as early as day 3 after inoculation, followed by αβ T cells at day 5. We then used bone marrow chimeras and fetal liver reconstitutions to create mice with an intact γδ T cell repertoire but one that was specifically deficient in the capacity to produce IFN-γ. Such mice had a higher incidence of tumor development, induced either with MCA or by inoculation of B16 melanoma cells, compared with mice with IFN-γ-competent γδ T cells. Moreover, genetic deficiency of γδ T cells resulted in impaired IFN-γ production by tumor antigen-triggered αβ T cell upon immunization with tumor lysate. These results demonstrate that γδ T cells can play a necessary role in tumor immunity through provision of an early source of IFN-γ that in turn may regulate the function of tumor-triggered αβ T cells.

Original languageEnglish (US)
Pages (from-to)433-442
Number of pages10
JournalJournal of Experimental Medicine
Volume198
Issue number3
DOIs
StatePublished - Aug 4 2003

Keywords

  • Cytokines
  • Immune regulation
  • Immunosurveillance
  • Tumor immunosurveillance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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