Service Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
Atreca, Redwood City, CA, United States.
Front Immunol. 2022 Aug 24;13:960120. doi: 10.3389/fimmu.2022.960120. eCollection 2022.
Optimal T follicular helper (Tfh) cells function is important to promote the development of germinal centers and maturation of high affinity antigen-specific B cells. We have found that the expression of CXCR3 defines distinct Tfh subsets: CXCR3 Th1-like Tfh cells mainly producing single IFN-γ and dual IL-21/IFN-γ and CXCR3 Th2-like Tfh cells mainly producing single IL-4 and dual IL-21/IL-4 cytokines. CXCR3 Th2-like Tfhs are significantly reduced during ongoing HIV replication. While the percentage of Th2-like Tfh cells correlates with that of total and cycling HIV-specific B cells, the percentage of CXCR3 Th1-like Tfhs correlates with HIV-specific B cells expressing T-bet and CXCR3. Of note, only IL-4 and IL-21 cytokines boosted efficient maturation of HIV-specific B cells while IFN-γ induced expression of T-bet and CXCR3 in B cells. Interestingly, total and HIV-specific CXCR3 B cells showed lower rate of somatic hypermutation, as compared to CXCR3 B cells. Therefore, the imbalance in Th2/Th1-like Tfhs affects B cell responses in viremic HIV infection.
最佳的滤泡辅助性 T 细胞（Tfh）功能对于促进生发中心的发育和高亲和力抗原特异性 B 细胞的成熟非常重要。我们发现，CXCR3 的表达定义了不同的 Tfh 亚群：CXCR3 Th1 样 Tfh 细胞主要产生单干扰素-γ和双白细胞介素-21/干扰素-γ，而 CXCR3 Th2 样 Tfh 细胞主要产生单白细胞介素-4 和双白细胞介素-21/白细胞介素-4 细胞因子。在持续的 HIV 复制过程中，CXCR3 Th2 样 Tfh 细胞显著减少。虽然 Th2 样 Tfh 细胞的百分比与总 HIV 特异性 B 细胞和循环 B 细胞的百分比相关，但 CXCR3 Th1 样 Tfh 细胞的百分比与表达 T-bet 和 CXCR3 的 HIV 特异性 B 细胞相关。值得注意的是，只有白细胞介素-4 和白细胞介素-21 细胞因子能够有效地促进 HIV 特异性 B 细胞的成熟，而干扰素-γ在 B 细胞中诱导 T-bet 和 CXCR3 的表达。有趣的是，与 CXCR3 B 细胞相比，总 HIV 特异性 CXCR3 B 细胞和 HIV 特异性 CXCR3 B 细胞的体细胞高频突变率较低。因此，Th2/Th1 样 Tfh 细胞的失衡会影响病毒血症 HIV 感染中的 B 细胞反应。
