Department of Biomedical Engineering, Cockrell School of Engineering, University of Texas at Austin, Austin, TX, United States.
Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States.
Front Immunol. 2022 May 6;13:859070. doi: 10.3389/fimmu.2022.859070. eCollection 2022.
Follicular-helper T cells (T) are an essential arm of the adaptive immune system. Although T were first discovered through their ability to contribute to antibody affinity maturation through co-stimulatory interactions with B cells, new light has been shed on their ability to remain a complex and functionally plastic cell type. Due to a lack sample availability, however, many studies have been limited to characterizing T in mice or non-canonical tissue types, such as peripheral blood. Such constraints have resulted in a limited, and sometimes contradictory, understanding of this fundamental cell type. One subset of T receiving attention in chronic infection are CXCR3-expressing T cells (CXCR3T) due to their abnormal accumulation in secondary lymphoid tissues. Their function and clonal relationship with other T subsets in lymphoid tissues during infection, however, remains largely unclear. We thus systematically investigated this and other subsets of T within untreated HIV-infected human lymph nodes using Mass CyTOF and a combination of RNA and TCR repertoire sequencing. We show an inflation of the CXCR3T compartment during HIV infection that correlates with a lower HIV burden. Deeper analysis into this population revealed a functional shift of CXCR3T away from germinal center T (GC-T), including the altered expression of several important transcription factors and cytokines. CXCR3T also upregulated cell migration transcriptional programs and were clonally related to peripheral T populations. In combination, these data suggest that CXCR3T have a greater tendency to enter circulation than their CXCR3 counterparts, potentially functioning through distinct modalities that may lead to enhanced defense.
滤泡辅助 T 细胞（T 细胞）是适应性免疫系统的重要组成部分。尽管 T 细胞最初是通过与 B 细胞的协同刺激相互作用来促进抗体亲和力成熟而被发现的，但人们对其保持复杂和功能可塑性细胞类型的能力有了新的认识。然而，由于缺乏样本可用性，许多研究仅限于在小鼠或非典型组织类型（如外周血）中对 T 细胞进行特征描述。这些限制导致对这种基本细胞类型的理解有限，有时甚至相互矛盾。在慢性感染中，一类受到关注的 T 细胞是 CXCR3 表达的 T 细胞（CXCR3T），因为它们在次级淋巴组织中异常积聚。然而，它们在感染期间与淋巴组织中其他 T 细胞亚群的功能和克隆关系在很大程度上仍不清楚。因此，我们使用 Mass CyTOF 和 RNA 和 TCR 受体库测序的组合，系统地研究了未经治疗的 HIV 感染人类淋巴结中的这些和其他 T 细胞亚群。我们发现，在 HIV 感染期间，CXCR3T 亚群的膨胀与 HIV 载量降低相关。对该群体的更深入分析表明，CXCR3T 的功能从生发中心 T（GC-T）发生转变，包括几个重要转录因子和细胞因子的表达改变。CXCR3T 还上调了细胞迁移转录程序，与外周 T 细胞群体具有克隆相关性。综合这些数据表明，CXCR3T 比其 CXCR3 对应物更倾向于进入循环，可能通过不同的方式发挥作用，从而增强防御。
