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Low-Frequency, Sustained CD4 T-Cell Responses Chlamydia trachomatis in Women: Predominant Targeting of Chlamydial Proteaselike Activity Factor (CPAF)
The Journal of Infectious Diseases ( IF 5.0 ) Pub Date : 2024-09-09 , DOI: 10.1093/infdis/jiae443
Yanli Li 1 , Joanna A Warren 1 , Taylor B Poston 2 , Genevieve Clutton 1 , Fiona R Shaw 1 , Shayla Z Conrad 1 , Yinyan Xu 1 , Xiaojing Zheng 2 , Kacy S Yount 2 , Catherine M O'Connell 2 , Harold C Wiesenfeld 3 , Toni Darville 2 , Nilu Goonetilleke 1
Affiliation  

Background Chlamydia trachomatis (CT) is a globally prevalent sexually transmitted infection that can result in pelvic inflammatory disease, ectopic pregnancy, and infertility in women. Currently, there is no prophylactic vaccine. Methods This study examined T-cell immunity in a cohort of women recently infected with CT. Participants were screened against peptides spanning 33 of 894 possible CT proteins, either ex vivo or using short-term cell lines. CT-specific T cells were characterized by interferon (IFN) γ enzyme-linked immunospot (ELISPOT) assay and flow cytometry. Results Ex vivo CT-specific T cells were rarely detected; however, in vitro expanded CT-specific T cells were detected by IFN-γ ELISPOT in 90% (27 of 30) of participants. Notably, >50% of participants had T-cell responses targeting chlamydial proteaselike activity factor (CPAF). T-cell epitopes were dispersed across the CPAF protein. Flow cytometric analysis of short-term cell lines found that CT-specific cells, mainly CD4, produced IFN-γ and tumor necrosis factor (TNF) α and were sustained over 12 months. Ex vivo analysis suggested that CT-specific T cells mostly exhibited a central memory phenotype. Conclusions Our results indicate that CT infection elicits low-frequency, persistent CD4 T-cell responses in most women and that the secreted protein, CPAF, is an immunoprevalent CT antigen. Altogether, these data support development and testing of CT vaccines that enhance CD4 T cells against CPAF.

中文翻译:


低频率、持续的 CD4 T 细胞反应女性沙眼衣原体:衣原体蛋白酶样活性因子 (CPAF) 的主要靶向



背景 沙眼衣原体 (CT) 是一种全球普遍的性传播感染,可导致女性盆腔炎、异位妊娠和不孕症。目前,没有预防性疫苗。方法 本研究检查了一组最近感染 CT 的女性的 T 细胞免疫力。参与者根据 894 种可能的 CT 蛋白中的 33 种的肽进行筛选,无论是离体还是使用短期细胞系。通过干扰素 (IFN) γ酶联免疫斑点 (ELISPOT) 测定和流式细胞术对 CT 特异性 T 细胞进行表征。结果 很少检测到离体 CT 特异性 T 细胞;然而,在 90% (30 例中的 27 例) 中,IFN γ ELISPOT 检测到体外扩增的 CT 特异性 T 细胞。值得注意的是,>50% 的参与者具有针对衣原体蛋白酶样活性因子 (CPAF) 的 T 细胞反应。T 细胞表位分散在 CPAF 蛋白上。短期细胞系的流式细胞术分析发现,CT 特异性细胞(主要是 CD4)产生 IFN-γ 和肿瘤坏死因子 (TNF) α,并持续超过 12 个月。离体分析表明,CT 特异性 T 细胞大多表现出中枢记忆表型。结论 我们的结果表明,CT 感染在大多数女性中会引起低频、持续的 CD4 T 细胞反应,并且分泌的蛋白 CPAF 是一种免疫普遍的 CT 抗原。总之,这些数据支持增强 CD4 T 细胞对抗 CPAF 的 CT 疫苗的开发和测试。
更新日期:2024-09-09
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