Kamanaka M, Yu P, Yasui T, Yoshida K, Kawabe T, Horii T, Kishimoto T, Kikutani H
Institute for Molecular and Cellular Biology, Research Institute for Microbial Diseases, Osaka University, Japan.
Immunity. 1996 Mar;4(3):275-81. doi: 10.1016/s1074-7613(00)80435-5.
CD40-deficient mice are susceptible to Leishmania major infection while their wild-type littermates can resolve the infection. Upon stimulation with L. major antigens, draining lymph node T cells of the mutant mice and the susceptible mice, BALB/c, secrete comparable amounts of IL-4. The mutant mice produce less IFN gamma than wild-type mice. The expression of IL-12 p40 mRNA was significantly lower in L. major antigen-stimulated cells of mutant mice than those of wild-type or BALB/c mice. In normal mice, engagement of CD40 activates macrophages to a leishmanicidal state in vitro in the presence of IFN gamma. The results suggest that the CD40-CD40 ligand interaction plays an important role in two critical steps of cell-mediated immunity to L. major infection: the generation of a Th1 response and activation of macrophages to a leishmanicidal state.
CD40缺陷小鼠易受硕大利什曼原虫感染，而它们的野生型同窝小鼠能够清除感染。用硕大利什曼原虫抗原刺激后，突变小鼠和易感小鼠BALB/c的引流淋巴结T细胞分泌的IL-4量相当。突变小鼠产生的IFNγ比野生型小鼠少。在突变小鼠中，经硕大利什曼原虫抗原刺激的细胞中IL-12 p40 mRNA的表达明显低于野生型或BALB/c小鼠。在正常小鼠中，CD40的结合在IFNγ存在的情况下可在体外将巨噬细胞激活至杀利什曼原虫状态。结果表明，CD40-CD40配体相互作用在针对硕大利什曼原虫感染的细胞介导免疫的两个关键步骤中起重要作用：Th1反应的产生以及巨噬细胞激活至杀利什曼原虫状态。
