协同刺激分子CD28与CD40L在鼠衣原体生殖道感染中的作用

The Roles of CD28-and CD40L-mediated Costimulation Played in Chlamydial Urogenital Infection in Mice

目的初步探讨由CD28和CD40L介导的协同刺激信号在衣原体感染中的作用。方法用1×104IFUs的沙眼衣原体鼠生物型(MoPn)经生殖道感染雌性C57BL/6 J野生型(wt)、CD28 KO、CD80/CD86 KO、CD40L KO及CD40 KO小鼠,免疫荧光法测定生殖道分泌物中衣原体包涵体的数量。初次感染后80天和115天,处死小鼠,分离生殖道,做病理检查;用衣原体EB刺激脾细胞,测定特异性细胞免疫应答水平。结果 CD40LKO及CD40 KO小鼠阴道带菌时间比wt、CD28 KO及CD80/CD86 KO组明显延长;而CD28 KO及CD80/CD86 KO小鼠在初次感染衣原体后,生殖道病理变化比其他组轻。脾细胞因子水平显示,CD40L KO及CD40 KO组IFN-γ产生量较其它组低。结论不同的协同刺激信号在抗衣原体感染中发挥不同的作用,其中CD28分子与保护性免疫无关,但与炎症损伤反应有关;而CD40L-CD40介导的协同刺激信号与衣原体保护性免疫有关。

Objective To investigate the roles of CD28 - and CD40L - mediated costimulation in the development of protective immunity and pathology during Chlamydial urogenital infection in mice. Methods wt and mice deficient in CD28, CD80/CD86, CIMOL and CD40 were inoculated intravaginally with 1 × 10 4 IFUs of live C. muridarum organisms. The number of Chlamydial inclusion bodies in vaginal swabs was measured by immunofluorescence assay. On D80 or D115 after primary infection, mice were sacrificed, the vaginal tract was isolated for pathology, and the spleen cells were collected for cytokines measurement. Results The Chlamydia shedding time of CD40L KO or CD40 KO mice was much lon- ger than wt, CD28 KO and CD80/CD86 KO mice. The genital tract pathology from the CD28 or CD80/CD86 - deficient mice was much less than wt after primary infection, but mice deficient in CD40 or CD40L developed similar pathology as wt mice. The results of Th2 （IL-4 ＆ IL- 5 ） and Th1 （IFN -γ） cytokines from the in vitro restimulated splenocyte culture supematants showed that both the wt mice and mice deficient in CD28 or CD80/CD86 produced significantly higher levels of IFN - γ than the CD40 or CD40L KO mice after primary infection. Conclusions Protective immunity and inflammatory pathologies induced during chtamydial infection can be mediated by distinct costimulation pathways with the CD28/B7 costimulation dispensable for protective immunity but required for inflammatory pathologies and the opposite for the CD40/CD40L costimulation system.