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

244 Citations (Scopus)

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

Fingerprint

Interferons
Immunity
T-Lymphocytes
Neoplasms
Methylcholanthrene
Immunologic Monitoring
Experimental Melanomas
Incidence
Neoplasm Antigens
Carcinogens
Melanoma
Immunization
Bone Marrow
Cytokines
Cell Line
Liver

Keywords

  • Cytokines
  • Immune regulation
  • Immunosurveillance
  • Tumor immunosurveillance

ASJC Scopus subject areas

  • Immunology

Cite this

γδ T cells provide an early source of interferon γ in tumor immunity. / Gao, Yunfei; Yang, Wancai; Pan, Meng; Scully, Eileen; Girardi, Michael; Augenlicht, Leonard H.; Craft, Joe; Yin, Zhinan.

In: Journal of Experimental Medicine, Vol. 198, No. 3, 04.08.2003, p. 433-442.

Research output: Contribution to journalArticle

Gao, Y, Yang, W, Pan, M, Scully, E, Girardi, M, Augenlicht, LH, Craft, J & Yin, Z 2003, 'γδ T cells provide an early source of interferon γ in tumor immunity', Journal of Experimental Medicine, vol. 198, no. 3, pp. 433-442. https://doi.org/10.1084/jem.20030584
Gao, Yunfei ; Yang, Wancai ; Pan, Meng ; Scully, Eileen ; Girardi, Michael ; Augenlicht, Leonard H. ; Craft, Joe ; Yin, Zhinan. / γδ T cells provide an early source of interferon γ in tumor immunity. In: Journal of Experimental Medicine. 2003 ; Vol. 198, No. 3. pp. 433-442.
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