DIFFERENTIAL REGULATION OF THE JANUS KINASE STAT PATHWAY AND BIOLOGICFUNCTION OF IL-13 IN PRIMARY HUMAN NK ACID T-CELLS - A COMPARATIVE-STUDY WITH IL-4

IL-13, a cytokine similar to IL-4, is a regulates 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-gamma secret ion. When NK cells were costimulated with IL-13 and IL-2, IL-13 genera lly resulted in two types of reactivity: IL-13 synergized with IL-2 to stimulate IFN-gamma production off it modestly inhibited IL-2-mediate d IFN-gamma production. In both types of donors, the effect of IL-13 o n IL-2-induced IFN-gamma production was in marked contrast to the stro ng inhibition seen with IL-4 in NK cells. Additionally, IL-13 suppress es IL-2-induced NK cytolytic and proliferative activities although les s efficiently than IL-2. In T cells, IL-13 inhibits anti-CD3 mAb/IL-2- or PHA-mediated IFN-gamma production and enhances cytolytic potential, Furthermore, we demonstrate that IL-13, like IL-4, induces distinct S TAT6-DNA binding complexes and tyrosine phosphosylation of STAT6 and J anus 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 N K and T cell activation and that IL-13 is a potent regulator of STAT6 and JAK3 in these cen types.