PDF(Pubmed)
Abstract：
We have demonstrated previously that TNF-α-producing CD8+ T cells mediate chlamydial pathogenesis, likely in an antigen (Ag)-specific fashion. Here we hypothesize that inhibition of Ag-specific CD8+ T cell response after immunization and/or challenge would correlate with protection against oviduct pathology induced by a protective vaccine regimen. Intranasal (i.n.) live chlamydial elementary body (EB), intramuscular (i.m.) live EB, or i.n. irrelevant antigen, bovine serum albumin (BSA), immunized animals induced near-total protection, 50% protection, or no protection, respectively against oviduct pathology following i.vag. C. muridarum challenge. In these models, we evaluated Ag-specific CD8+ T cell cytokine response at various time-periods after immunization or challenge. The results show protective efficacy of vaccine regimens correlated with reduction of Ag-specific CD8+ T cell TNF-α responses following i.vag. chlamydial challenge, not after immunization. Depletion of CD4+ T cells abrogated, whereas adoptive transfer of Ag-specific CD4+ T cells induced the significant reduction of Ag-specific CD8+ T cell TNF-α response after chlamydial challenge. In conclusion, protective anti-chlamydial vaccine regimens induce Ag-specific CD4+ T cell response that mediate early inhibition of pathogenic CD8+ T cell response following challenge and may serve as a predictive biomarker of protection against Chlamydia -induced chronic pathologies.
摘要：
我们以前已经证明，产生TNF-α的CD8+T细胞介导衣原体发病机制，可能以抗原（Ag）特异性方式。在这里，我们假设免疫和/或攻击后Ag特异性CD8+T细胞应答的抑制将与保护性疫苗方案诱导的针对输卵管病理的保护相关。鼻内（i.n.）活衣原体基本体（EB），肌内（i.m.）活EB，或i.n.无关抗原，牛血清白蛋白(BSA),免疫动物诱导几乎完全保护，50%保护,或者没有保护，分别针对i.vag后的输卵管病理学。c.muridarum挑战。在这些模型中,我们评估了免疫或攻击后不同时间段的Ag特异性CD8+T细胞细胞因子应答.结果显示疫苗方案的保护效力与在阴道后Ag特异性CD8+T细胞TNF-α应答的减少相关。衣原体挑战，免疫接种后没有。CD4+T细胞的耗竭被废除，而在衣原体攻击后，Ag特异性CD4+T细胞的过继转移诱导了Ag特异性CD8+T细胞TNF-α反应的显着降低。总之,保护性抗衣原体疫苗方案诱导Ag特异性CD4+T细胞应答,其在攻击后介导致病性CD8+T细胞应答的早期抑制,并且可以作为针对衣原体诱导的慢性病理的保护的预测性生物标志物。
