Tripp C S, Beckerman K P, Unanue E R
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Clin Invest. 1995 Apr;95(4):1628-34. doi: 10.1172/JCI117837.
The presence of soluble antigen-antibody complexes renders mice highly susceptible to infection with the intracellular pathogen Listeria monocytogenes. In this report we show that this inhibition is manifest at the level of the innate immune response and is mediated by IL-10. Like immuno-competent mice, mice with the severe combined immunodeficient mutation (SCID) injected with immune complexes died from a sublethal dose of L. monocytogenes. These mice were protected if pretreated with neutralizing antibodies to IL-10. In vitro, immune complexes stimulated IL-10 production by SCID splenocytes and splenic macrophages. Likewise, immune complexes inhibited TNF and IFN-gamma production by SCID splenocytes cultured with heat-killed-L. monocytogenes. This inhibition was reversed by neutralization of IL-10 but not IL-4 or TGF-beta. Immune complexes and rIL-10 inhibited cytokine production by SCID splenocytes if added before or simultaneously with heat-killed-L. monocytogenes. These data support a model in which immune complexes modulate host defense and the immune response by stimulating the production of IL-10 from macrophages.
可溶性抗原 - 抗体复合物的存在使小鼠对细胞内病原体单核细胞增生李斯特菌的感染高度敏感。在本报告中，我们表明这种抑制作用在先天免疫反应水平上表现出来，并且由白细胞介素 - 10（IL - 10）介导。与免疫 competent 小鼠一样，注射免疫复合物的严重联合免疫缺陷突变（SCID）小鼠死于亚致死剂量的单核细胞增生李斯特菌。如果用抗IL - 10的中和抗体进行预处理，这些小鼠会受到保护。在体外，免疫复合物刺激SCID脾细胞和脾巨噬细胞产生IL - 10。同样，免疫复合物抑制与热灭活的单核细胞增生李斯特菌一起培养的SCID脾细胞产生肿瘤坏死因子（TNF）和干扰素 - γ（IFN - γ）。这种抑制作用通过中和IL - 10而不是IL - 4或转化生长因子 - β（TGF - β）得以逆转。如果在热灭活的单核细胞增生李斯特菌之前或同时添加免疫复合物和重组IL - 10（rIL - 10），则它们会抑制SCID脾细胞产生细胞因子。这些数据支持一种模型，即免疫复合物通过刺激巨噬细胞产生IL - 10来调节宿主防御和免疫反应。
