High-Frequency, Functional HIV-Specific T-Follicular Helper and Regulatory Cells Are Present Within Germinal Centers in Children but Not Adults.
High-Frequency, Functional HIV-Specific T-Follicular Helper and Regulatory Cells Are Present Within Germinal Centers in Children but Not Adults.
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DOI：
10.3389/fimmu.2018.01975
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发表时间：
2018
影响因子：
7.3
通讯作者：
Leslie A
中科院分区：
文献类型：
--
作者：
Roider J;Maehara T;Ngoepe A;Ramsuran D;Muenchhoff M;Adland E;Aicher T;Kazer SW;Jooste P;Karim F;Kuhn W;Shalek AK;Ndung'u T;Morris L;Moore PL;Pillai S;Kløverpris H;Goulder P;Leslie A
广泛中和抗体（bnAbs）是预防HIV-1传播的有效手段。为了更好地了解hiv特异性bnAbs自然产生的机制，我们研究了儿童感染的血液和淋巴组织，因为强效bnAbs在儿童中的产生频率高于成人。与成人一样，HIV感染治疗中循环效应t -滤泡辅助细胞（TFH）的频率naïve儿童与中和广度相关。然而，在循环和少数扁桃体样本中也观察到儿童和成人之间的主要差异。在儿童中，TFH细胞在血液和淋巴组织生发中心都明显比成人丰富。其次，hiv特异性TFH细胞在儿童中比在成人淋巴组织中更常见，并分泌标志性的细胞因子IL-21，而hiv感染的成人则没有。第三，与成人相比，儿童淋巴组织中il -21分泌的hiv特异性TFH的富集伴随着TFH调节的增加，TFH调节通过更丰富的调节性滤泡t细胞和hiv特异性CXCR5+ CD8 t细胞实现。在儿童PBMC样本中也观察到调节与中和宽度之间的关系，并与中和宽度相关。从淋巴组织样本中没有匹配的中和数据。然而，受感染儿童和成人在hiv特异性TFH反应的大小、质量和调控方面的区别与儿童产生高频、强效bnAbs的优势能力是一致的。这些发现表明，设计用于诱导高频、强效bnAbs以预防成人HIV感染的下一代疫苗策略的最佳时机可能是在儿童时期。
Broadly neutralizing antibodies (bnAbs) against HIV-1 are an effective means of preventing transmission. To better understand the mechanisms by which HIV-specific bnAbs naturally develop, we investigated blood and lymphoid tissue in pediatric infection, since potent bnAbs develop with greater frequency in children than adults. As in adults, the frequency of circulating effector T-follicular helper cells (TFH) in HIV infected, treatment naïve children correlates with neutralization breadth. However, major differences between children and adults were also observed both in circulation, and in a small number of tonsil samples. In children, TFH cells are significantly more abundant, both in blood and in lymphoid tissue germinal centers, than in adults. Second, HIV-specific TFH cells are more frequent in pediatric than in adult lymphoid tissue and secrete the signature cytokine IL-21, which HIV-infected adults do not. Third, the enrichment of IL-21-secreting HIV-specific TFH in pediatric lymphoid tissue is accompanied by increased TFH regulation via more abundant regulatory follicular T-cells and HIV-specific CXCR5+ CD8 T-cells compared to adults. The relationship between regulation and neutralization breadth is also observed in the pediatric PBMC samples and correlates with neutralization breadth. Matching neutralization data from lymphoid tissue samples is not available. However, the distinction between infected children and adults in the magnitude, quality and regulation of HIV-specific TFH responses is consistent with the superior ability of children to develop high-frequency, potent bnAbs. These findings suggest the possibility that the optimal timing for next generation vaccine strategies designed to induce high-frequency, potent bnAbs to prevent HIV infection in adults would be in childhood.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
16.6
作者：
Arthur Huang KY;Chen MF;Huang YC;Shih SR;Chiu CH;Lin JJ;Wang JR;Tsao KC;Lin TY
通讯作者：
Lin TY
影响因子：
4.4
作者：
Good, Kim L.;Bryant, Vanessa L.;Tangye, Stuart G.
通讯作者：
Tangye, Stuart G.
DOI：
10.1136/mp.56.5.256
发表时间：
2003-10-01
期刊：
JOURNAL OF CLINICAL PATHOLOGY-MOLECULAR PATHOLOGY
影响因子：
--
作者：
Gilmour, KC;Walshe, D;Cale, CM
通讯作者：
Cale, CM
影响因子：
7.3
作者：
Hong JJ;Chang KT;Villinger F
通讯作者：
Villinger F