IL-13 production by NK cells: IL-13-producing NK and T cells are present in vivo in the absence of IFN-gamma.
In this study, we demonstrate that human NK cells, human NK clones, the human NK cell line (NK3.3), and a population of murine NK cells can produce the type 2 cytokine IL-13 in response to IL-2 or phorbol myristate acetate plus ionomycin. IL-2 rapidly induced new IL-13 mRNA and protein synthesis in the NK3.3 cell line. Six of 12 human NK clones tested produced IL-13 protein in response to IL-2 or phorbol myristate acetate and ionomycin. Intracellular analysis revealed that approximately 2% of human peripheral NK cells produced IL-13 protein in response to IL-2. Isolated NK cells from SCID and RAG-2 knockout (-/-) mice that lack T and B cells as well as normal mice also can produce IL-13 mRNA and protein in response to IL-2. We hypothesized that in the absence of IFN-gamma, IL-13-producing NK cells may predominate in vivo. Utilizing IFN-gamma knockout (-/-) mice as a model system, IL-2-activated liver NK and T cells expressed 10-fold more IL-13 and IL-5 mRNA and protein than normal controls following IL-2 treatment in vitro. These results suggest that in the absence of IFN-gamma, an IL-13- and IL-5-producing NK and T cells predominate in vivo. The existence of this cell type has important implications in innate immunity given that the balance between IFN-gamma and IL-13/IL-5-producing NK cells may influence the early development of a cell-mediated or humoral immune response.
Hoshino
T
T
Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201, USA.
Winkler-Pickett
R T
RT
Mason
A T
AT
Ortaldo
J R
JR
Young
H A
HA
D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000172:deficiency* / Q000235:genetics*; D018793:Interleukin-13 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology; D015848:Interleukin-5 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000276:immunology; D016131:Lymphocyte Subsets / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D009687:Nuclear Proteins; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000378:metabolism*; D019895:Transposases / Q000235:genetics
D004268:DNA-Binding Proteins; D018793:Interleukin-13; D007376:Interleukin-2; D015848:Interleukin-5; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D007371:Interferon-gamma; D019895:Transposases