Macatonia S E, Doherty T M, Knight S C, O'Garra A
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94303.
J Immunol. 1993 May 1;150(9):3755-65.
IL-10 has previously been shown to inhibit cytokine production by Th1 cells by blocking macrophage accessory cell function. In this study we demonstrate that dendritic cell-induced Th1 proliferation was unaffected by IL-10, whereas macrophage-stimulated proliferation was inhibited in the same system. In contrast dendritic cell induced IFN-gamma production by the Th1 clones was down-regulated by IL-10. Inasmuch as dendritic cells have been shown to be potent APC for T cells in primary responses we determined the effect of IL-10 on dendritic cell-induced proliferation and IFN-gamma production by CD4+ and CD8+ T cells. Dendritic cells were effective at stimulating both proliferation and IFN-gamma secretion of CD4+ or CD8+ T cells in a primary allogeneic mixed leukocyte response. In contrast, IL-10 markedly inhibited dendritic cell driven IFN-gamma production by purified CD4+ and CD8+ T cells. Down-regulation of dendritic cell-induced IFN-gamma production suggests a role for IL-10 in inhibiting the initiation of cell-mediated immune responses.
白细胞介素-10(IL-10)此前已被证明可通过阻断巨噬细胞辅助细胞功能来抑制Th1细胞产生细胞因子。在本研究中,我们证明树突状细胞诱导的Th1增殖不受IL-10影响,而在同一系统中巨噬细胞刺激的增殖则受到抑制。相反,树突状细胞诱导Th1克隆产生γ干扰素(IFN-γ)的过程被IL-10下调。鉴于树突状细胞在初次反应中已被证明是T细胞的有效抗原呈递细胞(APC),我们确定了IL-10对树突状细胞诱导的CD4+和CD8+ T细胞增殖及IFN-γ产生的影响。在初次异基因混合淋巴细胞反应中,树突状细胞能有效刺激CD4+或CD8+ T细胞的增殖及IFN-γ分泌。相比之下,IL-10显著抑制树突状细胞驱动的纯化CD4+和CD8+ T细胞产生IFN-γ。树突状细胞诱导的IFN-γ产生下调表明IL-10在抑制细胞介导的免疫反应启动中发挥作用。