Preservation of Peripheral T Follicular Helper Cell Function in HIV Controllers
Preservation of Peripheral T Follicular Helper Cell Function in HIV Controllers
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DOI：
10.1128/jvi.00497-17
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发表时间：
2017-07-01
影响因子：
5.4
通讯作者：
Streeck, Hendrik
中科院分区：
文献类型：
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作者：
Buranapraditkun, Supranee;Pissani, Franco;Streeck, Hendrik
高亲和力抗体的成熟过程是淋巴生发中心B细胞和滤泡辅助T(TFH)细胞之间复杂相互作用的结果。艾滋病毒感染会导致显著的慢性免疫激活、表型扭曲和由多年持续病毒复制驱动的炎症。高水平的病毒血症以及免疫激活和功能障碍已被证明对B细胞记忆隔间产生令人不安的影响，并导致B细胞耗尽。与直觉相反的是，与B细胞室的扰动相关的因素似乎有利于在少数HIV感染者中产生高亲和力成熟的环境特异性抗体。因此，HIV抗原血症对B细胞和TFH细胞相互作用的影响值得进一步探讨。因此，我们使用HIV Env gp120探针研究了不同病毒控制水平的个体中HIV特异性B细胞的免疫表型，并表征了外周血中匹配的T细胞的功能。虽然在HIV进展者中CXCR5(+)CD4(+)T细胞显著减少，但我们发现一小部分分泌gp120特异性白介素21(IL-21)的CXCR5(+)CD4(+)T细胞与gp120特异性B细胞频率显著相关。相比之下，无论是大量的CXCR5(+)CD4(+)T细胞还是其他HIV抗原特异性都与gp120特异性B细胞水平无关。来自精英控制者的HIV特异性B细胞在静止记忆亚群中显示出更多数量的gp120特异性B细胞，而进行者中的HIV特异性B细胞积累在组织样和激活的记忆亚群中。此外，精英控制者的CXCR5(+)CD4(+)T细胞表现出比HIV进展期细胞更强的体外诱导B细胞成熟和免疫球蛋白类转换的能力。在这项研究中，我们发现HIV Env特异性CXCR5(+)CD4(+)T细胞分泌IL-21与B细胞记忆表型和功能密切相关。此外，我们发现HIV控制者的免疫反应显示出比HIV进展者更好的内在帮助活性。
The maturation process of high-affinity antibodies is a result of intricate interactions between B cells and follicular helper T (Tfh) cells occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, and inflammation driven by years of continuous viral replication. High levels of viremia as well as immune activation and dysfunction have been demonstrated to have a perturbing impact on the B cell memory compartment and contribute to B cell exhaustion. Counterintuitively, the factors associated with perturbation of the B cell compartment seem to be favorable for the generation of highly affinity-matured Env-specific antibodies in a minority of HIV-infected individuals. Thus, the impact of HIV antigenemia on B cells and Tfh cell interactions warrants further exploration. We therefore studied immunophenotypes of HIV-specific B cells in individuals with differing levels of viral control using HIV Env gp120 probes and characterized the functionality of matched T cells in peripheral blood. While CXCR5(+) CD4(+) T cells were significantly diminished in HIV progressors, we found that a small subset of gp 120-specific interleukin-21 (IL-21)-secreting CXCR5(+) CD4(+) T cells were significantly associated with gp120-specific B cell frequencies. In contrast, neither bulk CXCR5(+) CD4(+) T cells nor other HIV antigen specificities were associated with gp120-specific B cell levels. HIV-specific B cells derived from elite controllers displayed greater amounts of gp120-specific B cells in the resting memory subset, whereas HIV-specific B cells in progressors accumulated in tissue-like and activated memory subsets. Furthermore, CXCR5(+) CD4(+) T cells from elite controllers showed a stronger ex vivo capacity to induce B cell maturation and immunoglobulin class switching than cells from HIV progressors.IMPORTANCE Dissecting the factors that are involved in B cell maturation and antibody development is important for HIV vaccine design. In this study, we found that HIV Env- specific CXCR5(+) CD4(+) T cells that secrete interleukin-21 are strongly associated with B cell memory phenotypes and function. Moreover, we found that the immune responses of HIV controllers showed intrinsically better helper activity than those of HIV progressors.