The effect of NK cell activation by tumor cells on antigen-specific antibody responses.
In addition to mediating direct cytotoxicity, NK cells can exert regulatory effects on specific immune responses. For example, injection of poly (I:C) can alter specific Ab responses, which is attributable to the production of IFN-gamma by NK cells. To test whether direct activation of NK cells can exert the same effect, we have injected, at the same time as Ag challenge, BCL1-C11 tumor cells, which are highly effective inducers of IFN-gamma production by NK cells. The results show a specific enhancement of the IgG2a response, which does not occur with a tumor (70Z/3) that does not induce IFN-gamma production. This enhancement is NK cell and IL-12 dependent. However, BCL1-C11 cells cannot directly induce IL-12 production in peritoneal exudate cells (PECs). On the other hand, PECs from tumor-treated mice produce IL-12 in response to LPS, suggesting that they are primed in vivo. Furthermore, the IL-12 production is NK cell and IFN-gamma dependent. These results indicate that if tumor cells can directly activate NK cells to produce IFN-gamma, this cytokine initiates an amplification loop by activating macrophages to produce IL-12, which in turn activates NK cells further, resulting in the alteration of the isotype distribution of specific Ab responses. Production of the appropriate Ab isotype should enhance Ab-dependent cellular cytotoxicity against targets mediated by NK cells, implicating their role(s) in the specific immune response as well as the initial nonspecific phase.
Koh
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Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235-9072, USA.
Yuan
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D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D014301:Trinitrobenzenes / Q000276:immunology; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D018985:Epitopes, B-Lymphocyte; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D008070:Lipopolysaccharides; D014301:Trinitrobenzenes; C048761:trinitrophenyl-lipopolysaccharide; D018664:Interleukin-12; D007371:Interferon-gamma