Cultured NK1.1+ CD4+ T cells produce large amounts of IL-4 and IFN-gamma upon activation by anti-CD3 or CD1.
NK1.1+ CD4+ T cells produce more IL-4 and IFN-gamma in response to stimulation with anti-CD3 than conventional CD4+ T cells that have been primed to be, respectively, Th2 or Th1 cells. Furthermore, NK1.1+ CD4+ T cells produce IL-4 even if cultured in the absence of IL-4, whereas conventional CD4+ T cells require IL-4 to develop into IL-4 producers. The IFN-gamma-producing capacity of NK1.1+ CD4+ T cells is enhanced by IL-12. In addition, NK1.1+ CD4+ T cells produce substantial amounts of IL-3, IL-5, and IL-10 upon anti-CD3 stimulation. NK1.1+ CD4+ T cells can be stimulated to produce IL-4 by culture with L cells expressing CD1 (L-CD1), but primary IL-4 production was rather slow and weak. Restimulation of L-CD1-activated NK1.1+ CD4+ T cells with L-CD1 gave rise to a much stronger and more rapid response, yielding IL-4 production comparable with anti-CD3 activation of cells initially primed with anti-CD3. L-CD1 stimulation of L-CD1-primed cells resulted in far less IFN-gamma than that elicited by anti-CD3 from cells that had been primed with anti-CD3, but such production is substantially increased by adding IL-12 to the culture. The differing patterns of cytokine production by NK1.1+ CD4+ T cells suggest that these cells may have complex effects on the priming of conventional T cells and may not simply drive such cells to the acquisition of a Th2 phenotype.
Chen
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Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Paul
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D000818:Animals; D000941:Antigens / Q000502:physiology*; D018949:Antigens, CD1 / Q000096:biosynthesis / Q000502:physiology*; D000950:Antigens, Ly; D000954:Antigens, Surface; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000235:genetics; D007739:L Cells; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016853:Muromonab-CD3 / Q000494:pharmacology*; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D014162:Transfection
D000941:Antigens; D018949:Antigens, CD1; D000950:Antigens, Ly; D000954:Antigens, Surface; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D016853:Muromonab-CD3; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D011993:Recombinant Fusion Proteins; D015847:Interleukin-4; D007371:Interferon-gamma