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Laboratory of Experimental Immunology,
Laboratory of Molecular Immunoregulation, Division of Basic Sciences;
Intramural Research Support Program, Science Applications International Corporation-Frederick; National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702
IL-13, a cytokine similar to IL-4, is a regulator of human B cell
and monocyte functions. Biologic effects of IL-13 on primary human NK
and T cells have not been well defined. We demonstrate that, in primary
NK cells, IL-13, but not IL-4, may induce low levels of IFN-
secretion. When NK cells were costimulated with IL-13 and IL-2, IL-13
generally resulted in two types of reactivity: IL-13 synergized with
IL-2 to stimulate IFN- production or it modestly inhibited
IL-2-mediated IFN- production. In both types of donors, the effect
of IL-13 on IL-2-induced IFN- production was in marked contrast to
the strong inhibition seen with IL-4 in NK cells. Additionally, IL-13
suppresses IL-2-induced NK cytolytic and proliferative activities
although less efficiently than IL-4. In T cells, IL-13 inhibits
anti-CD3 mAb/IL-2- or PHA-mediated IFN- production and enhances
cytolytic potential. Furthermore, we demonstrate that IL-13, like IL-4,
induces distinct STAT6-DNA binding complexes and tyrosine
phosphorylation of STAT6 and Janus kinase 3 (JAK3) in NK and T cells.
We observed that Abs directed against unique domains of STAT6 have
differential effects on complexes in T cells but not in NK cells,
suggesting different STAT6 isoforms. These findings show that IL-13 and
IL-4 have the ability to regulate NK and T cell activation and that
IL-13 is a potent regulator of STAT6 and JAK3 in these cell types.
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