Yu C R, Kirken R A, Malabarba M G, Young H A, Ortaldo J R
Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA.
J Immunol. 1998 Jul 1;161(1):218-27.
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-gamma 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-gamma production or it modestly inhibited IL-2-mediated IFN-gamma production. In both types of donors, the effect of IL-13 on IL-2-induced IFN-gamma 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-gamma 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.
白细胞介素-13（IL-13）是一种与白细胞介素-4（IL-4）相似的细胞因子，是人类B细胞和单核细胞功能的调节因子。IL-13对原代人自然杀伤细胞（NK细胞）和T细胞的生物学效应尚未明确界定。我们证明，在原代NK细胞中，IL-13而非IL-4可诱导低水平的γ干扰素分泌。当NK细胞与IL-13和IL-2共同刺激时，IL-13通常会产生两种反应类型：IL-13与IL-2协同刺激γ干扰素产生，或适度抑制IL-2介导的γ干扰素产生。在这两种类型的供体中，IL-13对IL-2诱导的γ干扰素产生的影响与NK细胞中IL-4所产生的强烈抑制形成鲜明对比。此外，IL-13可抑制IL-2诱导的NK细胞溶解和增殖活性，尽管其效率低于IL-4。在T细胞中，IL-13抑制抗CD3单克隆抗体/IL-2或植物血凝素（PHA）介导的γ干扰素产生，并增强细胞溶解潜能。此外，我们证明，与IL-4一样，IL-13在NK细胞和T细胞中诱导不同的信号转导和转录激活因子6（STAT6）-DNA结合复合物以及STAT6和Janus激酶3（JAK3）的酪氨酸磷酸化。我们观察到，针对STAT6独特结构域的抗体对T细胞中的复合物有不同影响，但对NK细胞中的复合物无影响，这表明存在不同的STAT6异构体。这些发现表明，IL-13和IL-4有能力调节NK细胞和T细胞的激活，并且IL-13是这些细胞类型中STAT6和JAK3的有效调节因子。
