Low Peripheral T Follicular Helper Cells in Perinatally HIV-Infected Children Correlate With Advancing HIV Disease.
Low Peripheral T Follicular Helper Cells in Perinatally HIV-Infected Children Correlate With Advancing HIV Disease.
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DOI：
10.3389/fimmu.2018.01901
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发表时间：
2018
影响因子：
7.3
通讯作者：
Khaitan A
中科院分区：
文献类型：
--
作者：
McCarty B;Mwamzuka M;Marshed F;Generoso M;Alvarez P;Ilmet T;Kravietz A;Ahmed A;Borkowsky W;Unutmaz D;Khaitan A
T滤泡辅助细胞（Tfh）对B细胞分化和抗原特异性抗体的产生至关重要。tfh介导的B细胞失调有助于削弱HIV感染中的B细胞反应。此外，淋巴结和外周血中的Tfh细胞构成了潜伏HIV储存库的很大一部分。关于围产期HIV感染对儿童Tfh细胞影响的数据有限。我们检测了hiv感染儿童外周血Tfh （pTfh）细胞频率和表型，以及它们与疾病进展、免疫激活和B细胞分化的关系。在肯尼亚的76名围产期HIV感染儿童队列中，包括43名treatment-naïve （ART -）和33名抗逆转录病毒治疗（ART+），以及42名健康对照（HIV -），我们使用多参数流式细胞术鉴定了记忆pTfh细胞、T细胞激活标记物和B细胞分化状态。ELISA法测定血浆可溶性CD163和肠道脂肪酸结合蛋白水平。接受抗逆转录病毒治疗的儿童与接受抗逆转录病毒治疗的儿童相比，pTfh细胞水平降低。无论治疗状态如何，HIV阳性儿童在pTfh细胞上的程序性细胞死亡蛋白1 （PD-1）表达较高。PD-1水平升高的低记忆pTfh细胞与HIV疾病进展相关，表现为HIV病毒载量、T细胞和单核细胞活化增加，CD4 %和CD4:CD8比值降低。抗逆转录病毒治疗，特别是在年轻时开始治疗，恢复pTfh细胞频率并消除与疾病进展的相关性，但未能降低pTfh细胞上的PD-1水平及其与CD4 T细胞百分比和激活的关联。在HIV+儿童中，B细胞亚群改变，naïve和静止记忆B细胞减少，激活和组织样记忆B细胞增加，与低记忆pTfh细胞频率相关。最后，HIV阳性儿童的CXCR5+ CD8 T细胞比例降低，这与低%CD4和CD4:CD8比值相关。HIV+儿童低记忆pTfh细胞频率与高PD-1表达与疾病状态恶化和激活和分化的B细胞谱相关。这种记忆紊乱的pTfh细胞群可能导致HIV阳性儿童的弱疫苗和HIV特异性抗体反应。恢复Tfh细胞的能力可能对新的儿科HIV治疗和疫苗策略很重要。
T follicular helper (Tfh) cells are crucial for B cell differentiation and antigen-specific antibody production. Dysregulation of Tfh-mediated B cell help weakens B cell responses in HIV infection. Moreover, Tfh cells in the lymph node and peripheral blood comprise a significant portion of the latent HIV reservoir. There is limited data on the effects of perinatal HIV infection on Tfh cells in children. We examined peripheral Tfh (pTfh) cell frequencies and phenotype in HIV-infected children and their associations with disease progression, immune activation, and B cell differentiation. In a Kenyan cohort of 76 perinatally HIV-infected children, comprised of 43 treatment-naïve (ART−) and 33 on antiretroviral therapy (ART+), and 42 healthy controls (HIV−), we identified memory pTfh cells, T cell activation markers, and B cell differentiation states using multi-parameter flow cytometry. Soluble CD163 and intestinal fatty acid-binding protein plasma levels were quantified by ELISA. ART− children had reduced levels of pTfh cells compared with HIV− children that increased with antiretroviral therapy. HIV+ children had higher programmed cell death protein 1 (PD-1) expression on pTfh cells, regardless of treatment status. Low memory pTfh cells with elevated PD-1 levels correlated with advancing HIV disease status, indicated by increasing HIV viral loads and T cell and monocyte activation, and decreasing %CD4 and CD4:CD8 ratios. Antiretroviral treatment, particularly when started at younger ages, restored pTfh cell frequency and eliminated correlations with disease progression, but failed to lower PD-1 levels on pTfh cells and their associations with CD4 T cell percentages and activation. Altered B cell subsets, with decreased naïve and resting memory B cells and increased activated and tissue-like memory B cells in HIV+ children, correlated with low memory pTfh cell frequencies. Last, HIV+ children had decreased proportions of CXCR5+ CD8 T cells that associated with low %CD4 and CD4:CD8 ratios. Low memory pTfh cell frequencies with high PD-1 expression in HIV+ children correlate with worsening disease status and an activated and differentiated B cell profile. This perturbed memory pTfh cell population may contribute to weak vaccine and HIV-specific antibody responses in HIV+ children. Restoring Tfh cell capacity may be important for novel pediatric HIV cure and vaccine strategies.
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T卵泡辅助细胞和对HIV-1感染儿童接受ART的对丙型肝炎病毒疫苗的抗体反应。
影响因子：
4.6
作者：
Bekele Y;Yibeltal D;Bobosha K;Andargie TE;Lemma M;Gebre M;Mekonnen E;Habtewold A;Nilsson A;Aseffa A;Howe R;Chiodi F
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影响因子：
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影响因子：
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通讯作者：
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