High-dose IL-2 and IL-15 enhance the in vitro priming of naive CD4+ T cells for IFN-gamma but have differential effects on priming for IL-4.
High-dose IL-2 and IL-15 enhance the in vitro priming of naive CD4+ T cells for IFN-gamma but have differential effects on priming for IL-4.
复制标题
高剂量 IL-2 和 IL-15 增强初始 CD4 T 细胞对 IFN-γ 的体外启动，但对 IL-4 的启动有不同的影响。
作者：
R. Seder
细胞因子在初始CD 4 + T细胞体外分化为产生IL-4或IFN-γ的细胞中起重要作用。需要IL-4和IL-2两者的存在来体外引发细胞的IL-4。使用来自TCR转基因小鼠的纯化的CD 4 +/LECAM-1high T细胞作为初始应答细胞，研究IL-15的作用以观察其在IL-4引发方面是否与IL-2类似地起作用。在IL-4和抗IL-2存在下培养的纯化的CD 4 + T细胞不能引发细胞产生IL-4。向这些相同的培养物中添加IL-15不能恢复IL-4的引发，表明IL-2和IL-15在产生IL-4的细胞的体外分化期间可能具有不同的功能特性。还检查了IL-15在IFN-γ引发中的作用。向引发培养物中添加高剂量的IL-15导致在再刺激后产生的IFN-γ的量显著增加。类似地，添加相对高剂量的IL-2也产生IFN-γ产生的显著增强;然而，如先前报道的，在引发培养物中IL-12的存在诱导IFN-γ产生的最大增加，使其成为生理情况下Th 1分化的主要控制者。最后，IL-15显示增加活化的CD 4 + T细胞母细胞的增殖，但不增加初始CD 4 + T细胞的增殖。此外，含有IL-12和IL-15的培养物显示出比单独的任一细胞因子更大的增殖，表明这些细胞因子之间的累加效应。
Cytokines play an important role for the in vitro differentiation of naive CD4+ T cells into IL-4- or IFN-gamma-producing cells. The presence of both IL-4 and IL-2 is required to prime cells for IL-4 in vitro. Using purified CD4+/LECAM-1high T cells from TCR transgenic mice as naive responder cells, the role of IL-15 was studied to see if it functioned similarly to IL-2 with regard to IL-4 priming. Purified CD4+ T cells cultured in the presence of IL-4 and anti-IL-2 failed to prime cells for IL-4 production. Addition of IL-15 to these same cultures could not restore priming for IL-4, suggesting that IL-2 and IL-15 may have different functional properties during the in vitro differentiation of IL-4-producing cells. The role of IL-15 in priming for IFN-gamma was also examined. The addition of high doses of IL-15 to priming cultures resulted in a striking increase in the amount of IFN-gamma produced following restimulation. Similarly, addition of a relatively high dose of IL-2 also produced a significant enhancement of IFN-gamma production; however, as previously reported, the presence of IL-12 in priming cultures induced the greatest increase in IFN-gamma production, leaving it as the predominant controller of Th1 differentiation in physiologic situations. Finally, IL-15 was shown to increase proliferation of activated CD4+ T cell blasts but not of naive CD4+ T cells. Moreover, cultures containing both IL-12 and IL-15 showed greater proliferation than either cytokine alone, suggesting an additive effect between these cytokines.