Beijing Key Laboratory for HIV/AIDS Research, Sino-French Joint Laboratory for Research on Humoral Immune Response to HIV Infection, Clinical and Research Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Department of Biology, Faculty of Science, Hong Kong Baptist University, Hong Kong, Hong Kong SAR, China.
Front Immunol. 2022 Feb 10;13:837921. doi: 10.3389/fimmu.2022.837921. eCollection 2022.
Interactions between T follicular helper (Tfh) cells and germinal center B cells are essential for the differentiation of B cells and specific antibody responses against HIV-1 infection. However, the extent to which HIV-1 infection affects the dynamic interplay between these two cell populations in the bloodstream remains unclear. In this study, the dynamics of circulating Tfh (cTfh) and B cells and their relationship in individuals with acute and chronic HIV-1 infection were investigated. Twenty-five study subjects were enrolled from the Beijing PRIMO clinical cohort, a prospective cohort of HIV-1-negative men who have sex with men (MSM) for the identification of cases of acute HIV-1 infection (AHI) at Beijing Youan Hospital, Capital Medical University. Individuals with AHI were selected at random. Matched samples were also collected and analyzed from the same patients with chronic HIV-1 infection. None of the study subjects received antiretroviral therapy during acute or chronic infection. Multicolor flow cytometry was used for the immunophenotypic and functional characterization of cTfh cell and B cell subsets. AHI resulted in increased proportions in bulk cTfh, ICOScTfh or IL-21ICOScTfh cells. In both acute and chronic infections, activated memory (AM), tissue-like memory (TLM), and plasmablast (PB) B cell levels were increased whilst resting memory (RM) and naïve mature (NM) B cell levels were decreased. Classical memory (CM) B cells were unaffected during infection. Association analyses showed that the levels of ICOScTfh and IL-21ICOScTfh cells were negatively correlated with those of AM, CM, RM cells, and positively correlated with those of NM cells in AHI but not chronic HIV-1 infection stage (CHI). Moreover, the frequency of IL-21ICOScTfh cells was also positively correlated with plasma HIV-1 viral load, and had an opposite association trend with CD4T cell count in AHI. Our data suggests that HIV-1 infection drives the expansion of cTfh cells, which in turn leads to perturbations of B cell differentiation through ICOS signaling during acute infection stage. These findings provide insight on the role of ICOS in the regulation of cTfh/B cell interaction during AHI and may potentially guide the design of effective strategies for restoring anti-HIV-1 immunity in the infected patients.
滤泡辅助 T 细胞（Tfh）与生发中心 B 细胞之间的相互作用对于 B 细胞的分化和针对 HIV-1 感染的特异性抗体反应至关重要。然而，HIV-1 感染对血流中这两种细胞群体之间动态相互作用的影响程度尚不清楚。在这项研究中，研究了急性和慢性 HIV-1 感染个体中循环滤泡辅助 T 细胞（cTfh）和 B 细胞的动态及其相互关系。从北京 PRIMO 临床队列中招募了 25 名研究对象，该队列是首都医科大学北京佑安医院前瞻性队列，招募的是 HIV-1 阴性的男男性行为者（MSM），目的是鉴定急性 HIV-1 感染（AHI）病例。随机选择 AHI 个体。还从具有慢性 HIV-1 感染的同一患者中采集并分析了匹配样本。在急性或慢性感染期间，研究对象均未接受抗逆转录病毒治疗。多色流式细胞术用于 cTfh 细胞和 B 细胞亚群的免疫表型和功能特征分析。AHI 导致 bulk cTfh、ICOScTfh 或 IL-21ICOScTfh 细胞的比例增加。在急性和慢性感染中，激活的记忆（AM）、组织样记忆（TLM）和浆母细胞（PB）B 细胞水平升高，而静止记忆（RM）和幼稚成熟（NM）B 细胞水平降低。感染期间经典记忆（CM）B 细胞不受影响。关联分析显示，在 AHI 中，ICOScTfh 和 IL-21ICOScTfh 细胞的水平与 AM、CM、RM 细胞的水平呈负相关，与 NM 细胞的水平呈正相关，但在慢性 HIV-1 感染阶段（CHI）则无此相关性。此外，IL-21ICOScTfh 细胞的频率也与血浆 HIV-1 病毒载量呈正相关，与 AHI 中 CD4+T 细胞计数呈负相关。我们的数据表明，HIV-1 感染驱动 cTfh 细胞的扩增，进而通过 ICOS 信号通路导致 B 细胞分化紊乱，在急性感染阶段。这些发现为 ICOS 在调节 AHI 期间 cTfh/B 细胞相互作用中的作用提供了见解，并可能为设计有效的策略来恢复感染患者的抗 HIV-1 免疫提供指导。
