Abnormal Shift in B Memory Cell Profile Is Associated With the Expansion of Circulating T Follicular Helper Cells via ICOS Signaling During Acute HIV-1 Infection.
Abnormal Shift in B Memory Cell Profile Is Associated With the Expansion of Circulating T Follicular Helper Cells via ICOS Signaling During Acute HIV-1 Infection.
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急性 HIV-1 感染期间 B 记忆细胞谱的异常变化与通过 ICOS 信号传导的循环滤泡辅助性 T 细胞的扩增相关
DOI：
10.3389/fimmu.2022.837921
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发表时间：
2022
影响因子：
7.3
通讯作者：
Su B
中科院分区：
文献类型：
--
作者：
Lu X;Zhang X;Cheung AKL;Moog C;Xia H;Li Z;Wang R;Ji Y;Xia W;Liu Z;Yuan L;Wang X;Wu H;Zhang T;Su B
T滤泡辅助细胞(TFH)和生发中心B细胞之间的相互作用对于B细胞的分化和抗HIV-1感染的特异性抗体应答是必不可少的。然而，HIV-1感染在多大程度上影响血流中这两个细胞群之间的动态相互作用仍不清楚。本研究探讨了急慢性HIV-1感染者外周血中Tfh(CTfh)和B细胞的动态变化及其相互关系。25名研究对象来自首都医科大学北京友安医院HIV-1阴性男男性行为者(MSM)的前瞻性队列北京Primo临床队列，用于鉴定急性HIV-1感染(AHI)病例。AHI患者是随机选择的。匹配的样本也来自相同的慢性HIV-1感染患者并进行分析。没有一名研究对象在急性或慢性感染期间接受抗逆转录病毒治疗。用多色流式细胞术检测cTfh细胞和B细胞亚群的免疫表型和功能。AHI导致cTfh、ICOS+cTfh或IL-21+ICOS+cTfh细胞比例增加。在急性和慢性感染中，激活记忆(AM)、组织样记忆(TLM)和浆母细胞(PB)B细胞水平升高，而静息记忆(RM)和幼稚成熟(NM)B细胞水平下降。经典记忆(CM)B细胞在感染过程中未受影响。相关分析显示，AHI患者ICOS+cTfh、IL-21+ICOS+cTfh细胞与AM、CM、RM细胞呈负相关，与NM细胞呈正相关，而与慢性HIV-1感染期(CHI)患者无相关性。AHI患者IL-21+ICOS+cTfh细胞频率与血浆HIV-1病毒载量呈正相关，与CD4+T细胞计数呈负相关趋势。我们的数据表明，HIV-1感染推动了cTfh细胞的扩张，进而导致在急性感染阶段通过ICOS信号扰乱B细胞的分化。这些发现为深入了解ICOS在AHI期间调节cTfh/B细胞相互作用中的作用提供了洞察力，并可能潜在地指导设计有效的策略来恢复感染患者的抗HIV-1免疫。
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, ICOS+cTfh or IL-21+ICOS+cTfh 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 ICOS+cTfh and IL-21+ICOS+cTfh 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-21+ICOS+cTfh cells was also positively correlated with plasma HIV-1 viral load, and had an opposite association trend with CD4+T 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.
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影响因子：
5.5
作者：
Hu, Zhiliang;Luo, Zhenwu;Wan, Zhuang;Wu, Hao;Li, Wei;Zhang, Tong;Jiang, Wei
通讯作者：
Jiang, Wei
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
5.4
作者：
Buranapraditkun, Supranee;Pissani, Franco;Streeck, Hendrik
通讯作者：
Streeck, Hendrik
影响因子：
--
作者：
Hutloff, A;B端chner, K;Kroczek, RA
通讯作者：
Kroczek, RA
影响因子：
6.4
作者：
Claireaux M;Galperin M;Benati D;Nouël A;Mukhopadhyay M;Klingler J;de Truchis P;Zucman D;Hendou S;Boufassa F;Moog C;Lambotte O;Chakrabarti LA
通讯作者：
Chakrabarti LA