Cross-talk between T cells and innate immune cells is crucial for IFN-gamma-dependent tumor rejection.
Though the importance of IFN-gamma in tumor immunity has been well-demonstrated, little is known about its source and how it is induced. By using various bone marrow chimeric mice, we show here that IFN-gamma essential for tumor immunity is solely produced by hemopoietic cells. Surprisingly, IFN-gamma derived from T cells was not necessary for tumor immunity in this model. In the immunized mice, in which only innate immune cells have the IFN-gamma-producing potential, tumors were efficiently rejected. The innate immune cells, such as NK1.1(+) cells and CD11b(+) cells, can provide sufficient amounts of IFN-gamma which requires, however, the help of T cells. The close cooperation between T cells and innate immune cells during tumor regression is likely mediated by IL-2. Together, our results clearly illustrate how T cells cooperate with innate immune cells for IFN-gamma-mediated tumor rejection and this may have important indications for clinical trials of tumor immunotherapy.
Li
Zhiguang
Z
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Pradera
Felicia
F
Kammertoens
Thomas
T
Li
Bing
B
Liu
Shubai
S
Qin
Zhihai
Z
D019264:Adoptive Transfer; D000818:Animals; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000096:biosynthesis; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055651:NK Cell Lectin-Like Receptor Subfamily B; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D011828:Radiation Chimera; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation
D000950:Antigens, Ly; D000954:Antigens, Surface; D039481:CD11b Antigen; D007376:Interleukin-2; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D007371:Interferon-gamma