Tadmori W, Zhang M, Beavis A J, Sullivan L M, Narula S K
Immunology Department, Schering-Plough Research Institute, Kenilworth, NJ 07033.
Cytokine. 1994 Sep;6(5):462-71. doi: 10.1016/1043-4666(94)90072-8.
The effect of IL-10 on T-cell activation by alloantigens in primary mixed lymphocyte reaction (MLR) was examined. IL-10 strongly suppressed proliferation and cytokine synthesis observed in this reaction. To determine the cytokine synthesis inhibition that was critical for the IL-10 induced suppression of proliferation in MLR, the effect of exogenous cytokines (IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IFN-gamma, or TNF-alpha) on this suppression was examined. None of these cytokines, when used at high concentration, was able to completely restore proliferation in the MLR to the levels observed in the absence of IL-10. However, IL-2 and TNF-alpha, when added alone at high concentration, could partially overcome the IL-10 induced suppression of proliferation in MLR. Moreover, when a combination of IL-2 and TNF-alpha was added at suboptimal doses to IL-10-suppressed MLR, complete restoration of the proliferative response was obtained. The ability of IL-10 to suppress proliferation in MLR was dependent on the type of cells used as stimulators. Thus, IL-10 suppressed proliferation in MLR when allogeneic normal peripheral blood mononuclear cells (PBMC), highly purified monocytes or B cells, were used, but not when B-cell lines were used as stimulators. Investigation of the effect of IL-10 on cytokine synthesis revealed that when B-cell lines were used as stimulators of MLR, IL-10 suppressed IFN-gamma and IL-2 synthesis but was unable to suppress TNF-alpha production. In contrast, CSA, which inhibited proliferation in MLR induced by B-cell lines, also inhibited TNF-alpha. IL-2 and IFN-gamma synthesis. Together these data suggest that the suppression of MLR by IL-10 requires the effective inhibition of both IL-2 and TNF-alpha production to suppress a synergy between these two cytokines.
研究了白细胞介素-10（IL-10）对初次混合淋巴细胞反应（MLR）中同种异体抗原激活T细胞的影响。IL-10强烈抑制该反应中观察到的增殖和细胞因子合成。为了确定对IL-10诱导的MLR增殖抑制至关重要的细胞因子合成抑制作用，研究了外源性细胞因子（IL-1α、IL-1β、IL-2、IL-4、IL-6、干扰素-γ或肿瘤坏死因子-α）对这种抑制作用的影响。当以高浓度使用这些细胞因子时，没有一种能够将MLR中的增殖完全恢复到无IL-10时观察到的水平。然而，当单独以高浓度添加IL-2和肿瘤坏死因子-α时，可以部分克服IL-10诱导的MLR增殖抑制。此外，当以次优剂量将IL-2和肿瘤坏死因子-α的组合添加到IL-10抑制的MLR中时，增殖反应得到完全恢复。IL-10抑制MLR增殖的能力取决于用作刺激物的细胞类型。因此，当使用同种异体正常外周血单个核细胞（PBMC）、高度纯化的单核细胞或B细胞时，IL-10抑制MLR中的增殖，但当使用B细胞系作为刺激物时则不然。对IL-10对细胞因子合成影响的研究表明，当使用B细胞系作为MLR的刺激物时，IL-10抑制干扰素-γ和IL-2合成，但无法抑制肿瘤坏死因子-α的产生。相比之下，环孢菌素A（CSA）抑制由B细胞系诱导的MLR中的增殖，也抑制肿瘤坏死因子-α、IL-2和干扰素-γ合成。这些数据共同表明，IL-10对MLR 的抑制需要有效抑制IL-2和肿瘤坏死因子-α的产生，以抑制这两种细胞因子之间的协同作用。
