South Texas Center for Emerging Infectious Diseases, Department of Biology, University of Texas at San Antonio, San Antonio, Texas 78249, USA.
Infect Immun. 2011 Jul;79(7):2928-35. doi: 10.1128/IAI.05022-11. Epub 2011 May 2.
The immunopathogenesis of Chlamydia trachomatis-induced oviduct pathological sequelae is not well understood. Mice genetically deficient in perforin (perforin(-/-) mice) or tumor necrosis factor alpha (TNF-α) production (TNF-α(-/-) mice) displayed comparable vaginal chlamydial clearance rates but significantly reduced oviduct pathology (hydrosalpinx) compared to that of wild-type mice. Since both perforin and TNF-α are effector mechanisms of CD8(+) T cells, we evaluated the role of CD8(+) T cells during genital Chlamydia muridarum infection and oviduct sequelae. Following vaginal chlamydial challenge, (i) mice deficient in TAP I (and therefore the major histocompatibility complex [MHC] I pathway and CD8(+) T cells), (ii) wild-type mice depleted of CD8(+) T cells, and (iii) mice genetically deficient in CD8 (CD8(-/-) mice) all displayed similar levels of vaginal chlamydial clearance but significantly reduced hydrosalpinx, compared to those of wild-type C57BL/6 mice, suggesting a role for CD8(+) T cells in chlamydial pathogenesis. Repletion of CD8(-/-) mice with wild-type or perforin(-/-), but not TNF-α(-/-), CD8(+) T cells at the time of challenge restored hydrosalpinx to levels observed in wild-type C57BL/6 mice, suggesting that TNF-α production from CD8(+) T cells is important for pathogenesis. Additionally, repletion of TNF-α(-/-) mice with TNF-α(+/+) CD8(+) T cells significantly enhanced the incidence of hydrosalpinx and oviduct dilatation compared to those of TNF-α(-/-) mice but not to the levels found in wild-type mice, suggesting that TNF-α production from CD8(+) T cells and non-CD8(+) cells cooperates to induce optimal oviduct pathology following genital chlamydial infection. These results provide compelling new evidence supporting the contribution of CD8(+) T cells and TNF-α production to Chlamydia-induced reproductive tract sequelae.
沙眼衣原体引起的输卵管病变的免疫发病机制尚不清楚。穿孔素（perforin(-/-) 小鼠）或肿瘤坏死因子 α（TNF-α）产生缺陷（TNF-α(-/-) 小鼠）的小鼠显示出类似的阴道沙眼衣原体清除率，但与野生型小鼠相比，输卵管病变（积水）明显减少。由于穿孔素和 TNF-α都是 CD8(+) T 细胞的效应机制，我们评估了 CD8(+) T 细胞在生殖道沙眼衣原体感染和输卵管后遗症中的作用。在阴道沙眼衣原体感染后，（i）缺乏 TAP I（因此主要组织相容性复合物 [MHC] I 途径和 CD8(+) T 细胞）的小鼠、（ii）耗尽 CD8(+) T 细胞的野生型小鼠和（iii）缺乏 CD8（CD8(-/-) 小鼠）的小鼠均显示出相似水平的阴道沙眼衣原体清除率，但与野生型 C57BL/6 小鼠相比，输卵管积水明显减少，表明 CD8(+) T 细胞在沙眼衣原体发病机制中起作用。在挑战时用野生型或穿孔素缺陷（perforin(-/-)）但不是 TNF-α 缺陷（TNF-α(-/-)）的 CD8(+) T 细胞补充 CD8(-/-) 小鼠可将输卵管积水恢复至野生型 C57BL/6 小鼠观察到的水平，表明 CD8(+) T 细胞产生的 TNF-α 对发病机制很重要。此外，用 TNF-α(+/+) CD8(+) T 细胞补充 TNF-α(-/-) 小鼠可显著增加输卵管积水和输卵管扩张的发生率，高于 TNF-α(-/-) 小鼠，但低于野生型小鼠，表明 CD8(+) T 细胞和非 CD8(+) 细胞产生的 TNF-α 合作，以诱导生殖道沙眼衣原体感染后的最佳输卵管病变。这些结果提供了令人信服的新证据，支持 CD8(+) T 细胞和 TNF-α 产生对沙眼衣原体引起的生殖道后遗症的贡献。
