Impaired Phenotype and Function of T Follicular Helper Cells in HIV-1-Infected Children Receiving ART
Impaired Phenotype and Function of T Follicular Helper Cells in HIV-1-Infected Children Receiving ART
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DOI：
10.1097/md.0000000000001125
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发表时间：
2015-07-01
期刊：
影响因子：
1.6
通讯作者：
Chiodi, Francesca
中科院分区：
文献类型：
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作者：
Bekele, Yonas;Amu, Sylvie;Chiodi, Francesca
滤泡辅助 T (Tfh) 细胞是特异性体液免疫反应发展的重要组成部分； HIV-1感染儿童中Tfh细胞的数量和生物学是否受损尚未研究。在接受抗逆转录病毒治疗（ART）和年龄匹配对照的HIV-1感染儿童的血液中测定了Tfh细胞和B细胞的频率、表型和功能。流式细胞术用于表征 Tfh 细胞和 B 细胞亚群的频率。 Tfh 细胞体外激活后测量细胞因子表达。在 HIV-1 感染儿童中发现记忆 Tfh 细胞频率降低 (P < 0.001)，并且这些细胞上程序性死亡 1 (PD-1) 和诱导性 T 细胞共刺激物 (ICOS) 的表达降低 (P P < 0.01)。激活后，HIV-1感染儿童中Tfh细胞表达IL-4（B细胞功能的重要细胞因子）的能力受损。HIV-1感染儿童的B细胞亚群与对照组存在显着差异：静息记忆（RM）B细胞的频率降低（P < 0.01），而耗尽记忆B细胞的频率增加（P < 0.001）。有趣的是，RM细胞的减少与记忆Tfh细胞的减少相关（P = 0.02）。我们的研究表明，Tfh细胞（建立适应性B细胞反应的关键细胞）的功能和表型在儿童HIV-1感染期间受损。记忆 Tfh 细胞的持续减少与 RM B 细胞频率的下降有关，从而在这些细胞类型的功能障碍特征之间建立了新的联系，这些细胞类型是建立体液免疫的主要参与者。
T follicular helper (Tfh) cells are important components in development of specific humoral immune responses; whether the number and biology of Tfh cells is impaired in HIV-1-infected children is not yet studied.The frequency, phenotype, and function of Tfh cells and B cells were determined in blood of HIV-1-infected children receiving antiretroviral therapy (ART) and age-matched controls. Flow cytometry was used to characterize the frequency of Tfh cells and B cell subsets. Cytokine expression was measured after in vitro activation of Tfh cells.A reduced frequency of memory Tfh cells (P < 0.001) was identified in HIV-1-infected children and, on these cells, a reduced expression of programmed death-1 (PD-1) and inducible T cell costimulator (ICOS) (P P < 0.01). Upon activation, the capacity of Tfh cells to express IL-4, an important cytokine for B cell function, was impaired in HIV-1-infected children.B cell subpopulations in HIV-1-infected children displayed significant differences from the control group: the frequency of resting memory (RM) B cells was reduced (P < 0.01) whereas the frequency of exhausted memory B cells increased (P < 0.001). Interestingly, the decline of RM cells correlated with the reduction of memory Tfh cells (P = 0.02).Our study shows that function and phenotype of Tfh cells, pivotal cells for establishment of adaptive B cell responses, are impaired during HIV-1 infection in children. A consistent reduction of memory Tfh cells is associated with declined frequencies of RM B cells, creating a novel link between dysfunctional features of these cell types, major players in establishment of humoral immunity.