MacDonald Andrew S, Patton Elisabeth A, La Flamme Anne C, Araujo Maria I, Huxtable Clive R, Bauman Beverley, Pearce Edward J
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
J Immunol. 2002 May 1;168(9):4643-9. doi: 10.4049/jimmunol.168.9.4643.
The role of CD40/CD154 interaction during infection has primarily focused on pathogens that drive inflammatory Th1 responses. In this study, we show that CD40/CD154 interaction is a fundamental requirement for Th2 response development to the parasitic helminth Schistosoma mansoni. Compared with infected wild-type mice, greatly reduced levels of Th2-associated cytokines were measured both in vitro and in vivo, and no IgE or IgG1 was detected in infected CD154(-/-) mice. In the absence of an overt Th2 response, no exaggerated Th1 response was mounted by CD154(-/-) mice. Infected CD154(-/-) mice suffered severe morbidity and mortality, even though parasitemias in wild-type and CD154(-/-) mice did not differ significantly. These data indicate that CD40/CD154 interaction is required to allow development of a Th2-dominated immune response to S. mansoni and support the view that failure to develop such a response can have fatal consequences.
CD40/CD154相互作用在感染过程中的作用主要集中于驱动炎性Th1反应的病原体。在本研究中，我们发现CD40/CD154相互作用是Th2反应针对寄生性蠕虫曼氏血吸虫发生发展的一项基本条件。与受感染的野生型小鼠相比，在体外和体内均检测到Th2相关细胞因子水平大幅降低，且在受感染的CD154(-/-)小鼠中未检测到IgE或IgG1。在缺乏明显Th2反应的情况下，CD154(-/-)小鼠未出现过度的Th1反应。受感染的CD154(-/-)小鼠出现严重发病和死亡，尽管野生型和CD154(-/-)小鼠的虫血症无显著差异。这些数据表明，CD40/CD154相互作用是对曼氏血吸虫产生以Th2为主导的免疫反应所必需的，并支持以下观点，即无法产生这种反应可能会导致致命后果。
