Activation of gamma delta T cells for production of IFN-gamma is mediated by bacteria via macrophage-derived cytokines IL-1 and IL-12.
Gamma delta T cells are found at sites of microbial infection and have been reported to proliferate in response to bacterial Ags. We show here that although the response by Listeria-elicited peritoneal gamma delta T cells to heat-killed bacteria in the presence of macrophage accessory cells may be partially mediated via the TCR, it is predominantly mediated via cytokines produced by the macrophages. Macrophage cytokines IL-12 and IL-1 synergize to induce some proliferation and considerable IFN-gamma production by peritoneal gamma delta T cells. This cytokine synergy pattern differs from that reported for NK cells, in which IL-12 in combination with either IL-2 or TNF-alpha induces NK cells to produce IFN-gamma. The combination of IL-12 and IL-1 provides a strong stimulus for IFN-gamma production by gamma delta T cells, but a relatively weak signal for proliferation. This is in contrast to the strong proliferative signal from the combination of IL-7 and IL-1 and the relatively weak stimulation of IFN-gamma production by the IL-7/IL-1 combination. Thus, there is differential regulation of NK and gamma delta T cells by cytokines and differential regulation of activation functions within the gamma delta T cell population by combinations of cytokines. These data provide evidence for a potentially important pathway for augmentation of IFN-gamma secretion at sites of infection where gamma delta T cells are found in abundance and where IFN-gamma may play a major role in the control of the infection.
Skeen
M J
MJ
Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
Ziegler
H K
HK
D000818:Animals; D016207:Cytokines / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D011090:Polyenes / Q000494:pharmacology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D020123:Sirolimus; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology
D016207:Cytokines; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D011090:Polyenes; D016692:Receptors, Antigen, T-Cell, gamma-delta; C079136:L 683590; D018664:Interleukin-12; D007371:Interferon-gamma; D020123:Sirolimus; D016559:Tacrolimus