IFN-gamma production and cytotoxicity of IL-2-activated murine NK cells are differentially regulated by MHC class I molecules.
Activation of NK cells by target cells leads to cytotoxicity as well as production of various cytokines including IFN-gamma. MHC class I molecules on target cells regulate NK cytotoxicity. However, little is known about the regulation of IFN-gamma production by NK cells. We examined the production of IFN-gamma in individual murine NK cells stimulated with tumor cell lines by flow cytometric analysis of intracellular IFN-gamma. Among several tumor lines tested, the rat basophilic leukemia line RBL-1 induced particularly high level of IFN-gamma production in IL-2-activated NK cells, whereas other lines, including the prototypic NK target YAC-1, induced very low or no IFN-gamma production. Transfection of murine classical MHC class I molecules into RBL-1 cells substantially inhibited IFN-gamma production. This inhibition of IFN-gamma production by MHC class I was independent of Ly-49 or CD94/NKG2A expression on NK cells. These results indicate that some target cells directly stimulate IL-2-activated NK cells and induce IFN-gamma production, but the requirements for the induction of IFN-gamma production seem different from those for NK cytotoxicity. Furthermore, similar to NK cytotoxicity, induction of IFN-gamma production is inhibited by MHC class I on stimulating cells. However, the MHC class I-specific receptors inhibiting IFN-gamma production are different from those for NK cytotoxicity.
Kubota
A
A
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
Lian
R H
RH
Lohwasser
S
S
Salcedo
M
M
Takei
F
F
D000818:Animals; D000950:Antigens, Ly; D001665:Binding Sites / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000378:metabolism / Q000502:physiology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000378:metabolism; D054340:Receptors, KIR; D055630:Receptors, NK Cell Lectin-Like; D014407:Tumor Cells, Cultured
D000950:Antigens, Ly; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D055630:Receptors, NK Cell Lectin-Like; D007371:Interferon-gamma