Center for Microbial Interface Biology, The Ohio State University, Columbus, OH 43210, USA.
Cell Immunol. 2011;271(1):53-61. doi: 10.1016/j.cellimm.2011.06.002. Epub 2011 Jun 12.
The in vitro immune responses to mycobacterial antigens have been linked to the H-2 loci in mice. We evaluated in vitro and in vivo immune responses during early Mycobacterium tuberculosis (M.tb) pulmonary infection of C57BL/6 (H-2(b)), C57BL/6 (H-2(k)), CBA/J (H-2(k)), and C3H/HeJ (H-2(k)) mice to determine H-2(k)-dependent and -independent effects. H-2(k)-dependent effects included delayed and diminished Ag85-specific Th1 cell priming, a reduced frequency of Ag85-specific IFN-γ producing cells, reduced IFN-γ protein in vivo, and increased M.tb lung burden as demonstrated by C57BL/6 H-2(k) mice vs. C57BL/6 mice. H-2(k)-independent factors controlled the amount of Ag85-specific IFN-γ produced by each cell, T cell numbers, granuloma size, and lymphocytic infiltrates in the lungs. Overall, these results suggest that an H-2(k)-dependent suboptimal generation of Ag85-specific cells impairs control of early M.tb growth in the lungs. H-2(k)-independent factors influence the potency of IFN-γ producing cells and immune cell trafficking during pulmonary M.tb infection.
结核分枝杆菌（Mycobacterium tuberculosis，M.tb）感染早期，小鼠的体外和体内免疫反应与 MHC Ⅱ类基因 H-2 紧密相关。我们评估了 C57BL/6（H-2(b)）、C57BL/6（H-2(k)）、CBA/J（H-2(k)）和 C3H/HeJ（H-2(k)）这 4 种不同 MHC Ⅱ类基因背景的小鼠的早期肺部 M.tb 感染的体外和体内免疫反应，以确定 H-2(k)依赖性和非依赖性效应。H-2(k)依赖性效应包括 Ag85 特异性 Th1 细胞初始反应的延迟和减弱，Ag85 特异性 IFN-γ 产生细胞的频率降低，体内 IFN-γ 蛋白减少，以及 M.tb 肺部负荷增加，这在 C57BL/6 H-2(k)小鼠与 C57BL/6 小鼠的对比中得到了证明。而非 H-2(k)依赖性因素控制了每个细胞产生的 Ag85 特异性 IFN-γ的量、T 细胞数量、肉芽肿大小和肺部淋巴细胞浸润。总的来说，这些结果表明，Ag85 特异性细胞的 H-2(k)依赖性生成不足会损害肺部早期 M.tb 生长的控制。非 H-2(k)依赖性因素影响肺部 M.tb 感染期间 IFN-γ 产生细胞的效力和免疫细胞的迁移。
