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Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702
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
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-
, IL-13-producing NK cells
may predominate in vivo. Utilizing IFN-
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-
, 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-
and
IL-13/IL-5-producing NK cells may influence the early development of a
cell-mediated or humoral immune response.
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