Groux H, Cottrez F, Rouleau M, Mauze S, Antonenko S, Hurst S, McNeil T, Bigler M, Roncarolo M G, Coffman R L
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304, USA.
J Immunol. 1999 Feb 1;162(3):1723-9.
IL-10 is a cytokine secreted by a wide variety of cells type that has pleiotropic stimulatory and suppressive activities on both lymphoid and myeloid cells in vitro. To analyze the consequences of high IL-10 secretion by APCs in immune responses, we produced transgenic mice expressing human IL-10 directed by the MHC class II Ea promoter. Despite alterations in the development of T and B cells, no gross abnormalities were detected in peripheral lymphocyte populations or serum Ig levels. However, when immunized using conditions that give either a Th2-type or a Th1-type response, IL-10 transgenic mice failed to mount a significant T or B cell immune response to OVA. IL-10 transgenic mice were also highly susceptible to infection with intracellular pathogens like Listeria monocytogenes or Leishmania major, in contrast to IL-10 transgenic mice, where the transgene was express in T cells. Finally, the recently described stimulatory effect of IL-10 on CD8+ T cells was confirmed by the ability of IL-10 transgenic mice to limit the growth of immunogenic tumors by a CTL-mediated mechanism. These results demonstrate, that, depending on the type of immune response, IL-10 can mediate immunosuppressive or immunostimulatory activities in vivo.
白细胞介素-10（IL-10）是一种由多种细胞类型分泌的细胞因子，在体外对淋巴细胞和髓细胞具有多效性刺激和抑制活性。为了分析抗原呈递细胞（APC）高分泌IL-10在免疫反应中的后果，我们制备了由MHC II类Ea启动子指导表达人IL-10的转基因小鼠。尽管T细胞和B细胞的发育发生了改变，但在外周淋巴细胞群体或血清免疫球蛋白水平上未检测到明显异常。然而，当使用引发Th2型或Th1型反应的条件进行免疫时，IL-10转基因小鼠未能对卵清蛋白（OVA）产生显著的T细胞或B细胞免疫反应。与转基因在T细胞中表达的IL-10转基因小鼠相比，IL-10转基因小鼠也极易受到细胞内病原体如单核细胞增生李斯特菌或硕大利什曼原虫的感染。最后，IL-10转基因小鼠通过CTL介导的机制限制免疫原性肿瘤生长的能力证实了最近描述的IL-10对CD8 + T细胞的刺激作用。这些结果表明，根据免疫反应的类型，IL-10在体内可介导免疫抑制或免疫刺激活性。
