Padigel Udaikumar M, Kim Nacksung, Choi Yongwon, Farrell Jay P
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Immunol. 2003 Nov 15;171(10):5437-41. doi: 10.4049/jimmunol.171.10.5437.
Blockade of TNF-related activation-induced cytokine (TRANCE)-receptor activator of NF-kappaB (RANK) interaction reverses healing in CD40L(-/-) mice infected with Leishmania major. Although previous studies demonstrated a requirement for CD40-CD40L interaction in production of IL-12 and the development of resistance to Leishmania infection, we recently showed that CD40L(-/-) mice control infection when inoculated with low numbers of parasites and that cells from these mice produce IL-12. Here, we show that in vivo treatment with a TRANCE receptor fusion protein results in a decrease in numbers of IL-12 producing cells as well as a shift from a dominant Th1 to Th2 type response in infected mice. These results demonstrate that CD40L(-/-) mice use the TRANCE-RANK costimulatory pathway to promote IL-12 production and the activation of a protective Th1 type response.
肿瘤坏死因子相关激活诱导细胞因子（TRANCE）-核因子κB受体激活剂（RANK）相互作用的阻断可逆转感染硕大利什曼原虫的CD40L（-/-）小鼠的愈合。尽管先前的研究表明CD40-CD40L相互作用在白细胞介素-12（IL-12）产生以及对利什曼原虫感染的抗性发展中是必需的，但我们最近发现，当接种少量寄生虫时，CD40L（-/-）小鼠能够控制感染，并且这些小鼠的细胞能产生IL-12。在此，我们表明，用TRANCE受体融合蛋白进行体内治疗会导致感染小鼠中产生IL-12的细胞数量减少，以及从占主导地位的Th1型反应向Th2型反应转变。这些结果表明，CD40L（-/-）小鼠利用TRANCE-RANK共刺激途径来促进IL-12的产生以及保护性Th1型反应的激活。
