Campbell K A, Ovendale P J, Kennedy M K, Fanslow W C, Reed S G, Maliszewski C R
Department of Cellular Immunology, Immunex Corporation, Seattle, Washington 98101, USA.
Immunity. 1996 Mar;4(3):283-9. doi: 10.1016/s1074-7613(00)80436-7.
The CD40-CD40 ligand (CD40L) signaling process is a pivotal component of multiple immunoregulatory pathways. Although the role that CD40L plays in humoral immune responses is fairly well defined, its function(s) in cell-mediated responses in vivo has not been established. We investigated this issue by assessing the course of Leishmania major infection in CD40L knockout (CD40LKO) mice that were generated on a resistant background. In response to parasite challenge, CD40LKO mice developed ulcerating cutaneous lesions and failed to mount a vigorous Th1-like response. The impaired Th1-like response appears to be related to a defect in the ability of CD40LKO T cells to induce the production of IL-12 from macrophages. Treatment with exogenous IL-12 prevented disease progression in CD40LKO mice, and administration of recombinant CD40L provided partial protection against infection. Thus, a protective cell-mediated immune response to L. major appears to be dependent upon CD40L-induced IL-12 secretion by antigen-presenting cells.
CD40-CD40配体（CD40L）信号传导过程是多种免疫调节途径的关键组成部分。尽管CD40L在体液免疫反应中的作用已相当明确，但其在体内细胞介导反应中的功能尚未确定。我们通过评估在抗性背景下产生的CD40L基因敲除（CD40LKO）小鼠中利什曼原虫主要感染的过程来研究这个问题。响应寄生虫攻击，CD40LKO小鼠出现溃疡性皮肤病变，并且未能产生强烈的Th1样反应。受损的Th1样反应似乎与CD40LKO T细胞诱导巨噬细胞产生IL-12的能力缺陷有关。用外源性IL-12治疗可防止CD40LKO小鼠的疾病进展，给予重组CD40L可提供部分抗感染保护。因此，对利什曼原虫主要感染的保护性细胞介导免疫反应似乎依赖于CD40L诱导抗原呈递细胞分泌IL-12。
