INTERLEUKIN-10 INHIBITS ALLOGENEIC PROLIFERATIVE AND CYTOTOXIC T-CELL RESPONSES GENERATED IN PRIMARY MIXED LYMPHOCYTE-CULTURES
INTERLEUKIN-10 INHIBITS ALLOGENEIC PROLIFERATIVE AND CYTOTOXIC T-CELL RESPONSES GENERATED IN PRIMARY MIXED LYMPHOCYTE-CULTURES
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DOI：
10.1093/intimm/4.12.1389
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发表时间：
1992-12-01
影响因子：
4.4
通讯作者：
RONCAROLO, MG
中科院分区：
文献类型：
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作者：
BEJARANO, MT;MALEFYT, RD;RONCAROLO, MG
研究了IL-10对原代混合淋巴细胞（MLCs）产生同种异体反应性的影响。IL-10以剂量依赖性方式抑制同种异体抗原诱导的增殖反应。当IL-10在培养开始时加入时，抑制效果最大，这表明它在T细胞激活的早期阶段起作用。在中和的抗IL-10单抗存在下，增殖反应增强，表明内源性产生的IL-10抑制原代MLC的增殖。无论使用辐照的异体外周血单核细胞、纯化的单核细胞还是新鲜分离的B细胞作为刺激细胞，均观察到IL-10的抑制作用。CD4+和CD8+ T细胞亚群的增殖均受到类似程度的抑制。高浓度的外源IL-2只能最低限度地恢复增殖反应，这表明IL-10的作用不仅仅是由于抑制IL-2的合成。此外，原代MLCs中IL-2、干扰素(IFN)- γ、IL-6、粒细胞巨噬细胞集落刺激因子和肿瘤坏死因子- α的产生被IL-10减少，在抗IL-10单抗存在下增加。在ifn - γ的产生上观察到最强的影响。虽然IL-10降低了增殖反应，但在IL-10处理和对照培养中，CD3+CD4+和CD3+CD8+ T细胞的比例保持不变，但通过CD25和HLA-DR表达判断，活化CD3+ T细胞的百分比持续降低。同种异体细胞毒性的产生也被IL-10抑制，并在抗IL-10单抗存在下增强。这些数据表明IL-10在体外对异体反应具有重要的调控作用。
The effects of IL-10 on the generation of alloreactivity in primary mixed lymphocyte cultures (MLCs) were investigated. IL-10 inhibited in a dose-dependent fashion the alloantigen-induced proliferative responses. The suppressive effect was maximal when IL-10 was added at the beginning of the cultures, suggesting that it acts on the early stages of T cell activation. The proliferative responses were enhanced in the presence of a neutralizing anti-IL-10 mAb, indicating that endogenously produced IL-10 suppresses proliferation in primary MLC. The inhibitory effects of IL-10 were observed irrespective of whether irradiated allogeneic peripheral blood mononuclear cells, purified monocytes or freshly isolated B cells were used as stimulator cells. The proliferation of both the CD4+ and CD8+ T cell subsets was inhibited to a similar extent. The reduced proliferative responses were only minimally restored by high concentrations of exogenous IL-2, indicating that the effects of IL-10 are not exclusively due to inhibition of IL-2 synthesis. Furthermore, the production of IL-2, interferon (IFN)-gamma, IL-6, granulocyte macrophage colony stimulating factor, and tumor necrosis factor-alpha in primary MLCs was diminished by IL-10 and enhanced in the presence of anti-IL-10 mAb. The strongest effects were observed on the production of IFN-gamma. Although IL-10 reduces the proliferative responses, the ratios of CD3+CD4+ and CD3+CD8+ T cells remained the same in IL-10 treated and control cultures, yet the percentages of activated CD3+ T cells, as judged by CD25 and HLA-DR expression, were consistently reduced. The generation of allospecific cytotoxicity was also inhibited by IL-10 and enhanced in the presence of anti-IL-10 mAb. These data indicate that IL-10 has important regulatory effects on allogeneic responses in vitro.