Soong L, Xu J C, Grewal I S, Kima P, Sun J, Longley B J, Ruddle N H, McMahon-Pratt D, Flavell R A
Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8011, USA.
Immunity. 1996 Mar;4(3):263-73. doi: 10.1016/s1074-7613(00)80434-3.
To study the role of CD40 ligand (CD40L) in the host immune responses against intracellular pathogens, we infected CD40L knockout (CD40L-/-) mice with Leishmania amazonensis. Although wild-type mice were susceptible to infection and developed progressive ulcerative lesions, tissue parasite burdens in CD40L-/- mice were significantly higher. This heightened susceptibility to infection was associated with an impaired T cell and macrophage activation and altered inflammatory response, as reflected by low levels of IFN gamma, lymphotoxin-tumor necrosis factor (LT-TNF), and nitric oxide (NO) production. Furthermore, CD40L-/- mice failed to generate a protective immune response after immunization. These results indicate an essential role of cognate CD40-CD40L interactions in the generation of cellular immune responses against an intracellular parasite.
为研究CD40配体（CD40L）在宿主针对细胞内病原体的免疫反应中的作用，我们用亚马逊利什曼原虫感染了CD40L基因敲除（CD40L-/-）小鼠。虽然野生型小鼠易受感染并出现进行性溃疡性病变，但CD40L-/-小鼠体内的组织寄生虫负荷显著更高。这种对感染的易感性增加与T细胞和巨噬细胞激活受损以及炎症反应改变有关，表现为干扰素γ、淋巴毒素-肿瘤坏死因子（LT-TNF）和一氧化氮（NO）产生水平较低。此外，CD40L-/-小鼠在免疫后未能产生保护性免疫反应。这些结果表明同源CD40-CD40L相互作用在针对细胞内寄生虫的细胞免疫反应产生中起重要作用。
