Zhou Y, Kurihara T, Ryseck R P, Yang Y, Ryan C, Loy J, Warr G, Bravo R
Department of Oncology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA.
J Immunol. 1998 Apr 15;160(8):4018-25.
The CC-chemokine receptor CCR5 has been shown to be the major coreceptor for HIV-1 entry into cells, and humans with homozygous mutation in the ccr5 gene are highly resistant to HIV-1 infection, despite the existence of many other HIV-1 coreceptors. To investigate the physiologic function of CCR5 and to understand the cellular mechanisms of these clinical observations, we generated a CCR5-deficient mouse model (ccr5[-/-]) by targeted deletion of the ccr5 gene. We found that although developed normally in a pathogen-free environment, CCR5-deficient mice showed reduced efficiency in clearance of Listeria infection and exert a protective effect against LPS-induced endotoxemia, reflecting a partial defect in macrophage function. In addition, CCR5-deficient mice had an enhanced delayed-type hypersensitivity reaction and increased humoral responses to T cell-dependent antigenic challenge, indicating a novel role of CCR5 in down-modulating T cell-dependent immune response.
CC趋化因子受体CCR5已被证明是HIV-1进入细胞的主要共受体，尽管存在许多其他HIV-1共受体，但ccr5基因纯合突变的人对HIV-1感染具有高度抗性。为了研究CCR5的生理功能并了解这些临床观察结果的细胞机制，我们通过靶向缺失ccr5基因生成了CCR5缺陷小鼠模型（ccr5[-/-]）。我们发现，尽管在无病原体环境中正常发育，但CCR5缺陷小鼠清除李斯特菌感染的效率降低，并对LPS诱导的内毒素血症发挥保护作用，这反映了巨噬细胞功能的部分缺陷。此外，CCR5缺陷小鼠的迟发型超敏反应增强，对T细胞依赖性抗原攻击的体液反应增加，表明CCR5在下调T细胞依赖性免疫反应中具有新作用。
