Gamma delta T cells provide an early source of interferon gamma in tumor immunity.
Interferon (IFN)-gamma is necessary for tumor immunity, however, its initial cellular source is unknown. Because gammadelta T cells primarily produce this cytokine upon activation, we hypothesized that they would provide an important early source of IFN-gamma in tumor immunosurveillance. To address this hypothesis, we first demonstrated that gammadelta 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, gammadelta T cells were recruited to the site of tumor as early as day 3 after inoculation, followed by alphabeta T cells at day 5. We then used bone marrow chimeras and fetal liver reconstitutions to create mice with an intact gammadelta T cell repertoire but one that was specifically deficient in the capacity to produce IFN-gamma. 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-gamma-competent gammadelta T cells. Moreover, genetic deficiency of gammadelta T cells resulted in impaired IFN-gamma production by tumor antigen-triggered alphabeta T cell upon immunization with tumor lysate. These results demonstrate that gammadelta T cells can play a necessary role in tumor immunity through provision of an early source of IFN-gamma that in turn may regulate the function of tumor-triggered alphabeta T cells.
Gao
Yunfei
Y
Section of Rheumatology, Yale School of Medicine, 300 Cedar Street, CAB Building Room S517, New Haven, CT 06520, USA.
Yang
Wancai
W
Pan
Meng
M
Scully
Eileen
E
Girardi
Michael
M
Augenlicht
Leonard H
LH
Craft
Joe
J
Yin
Zhinan
Z
D000818:Animals; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018183:Transplantation Chimera; D014407:Tumor Cells, Cultured
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018664:Interleukin-12; D007371:Interferon-gamma