Impaired peripheral blood T-follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1/09 vaccine
Impaired peripheral blood T-follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1/09 vaccine
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DOI：
10.1182/blood-2011-12-396648
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发表时间：
2012-08-02
期刊：
影响因子：
20.3
通讯作者：
Pahwa, Savita
中科院分区：
文献类型：
--
作者：
Pallikkuth, Suresh;Parmigiani, Anita;Pahwa, Savita
在生发中心反应中，抗体分泌浆细胞的产生主要依赖于CD4T滤泡辅助细胞(TFH)。生发中心TFH细胞与循环中的CXCR5(+)CD4T细胞具有相同的功能特性，在此称为外周TFH(PTFH)细胞。由于抗体产生不足和CD4T细胞丢失是公认的HIV感染的特征，在本研究中，我们研究了25名接受抗逆转录病毒治疗的HIV感染患者的pTFH细胞。PTFH频率在患者和健康对照组(HCS)中相同，这些细胞表现出中枢记忆表型。在2009年H1N1流感暴发期间，该组中的16名患者和8名HC接种了单剂H1N1/09流感疫苗。在疫苗应答者(n=8)和HCS中，pTFH细胞在第4周(T2)经H1N1刺激的PBMC培养上清液中IL-21和CXCL13分泌增加。这些变化在疫苗无效者(n=8)中未见。在共培养实验中，分离的pTFH细胞仅在疫苗应答者中支持HIN1刺激的自体B细胞产生免疫球蛋白G。在T2时，pTFH的频率与记忆B细胞、血清H1N1抗体效价和Ag诱导的IL-21分泌相关。PTFH细胞的特性可能为疫苗诱导的抗体反应的细胞决定因素提供更多的洞察力，这可能与疫苗设计相关。(血。2012年；120(5)：985-993)
The generation of Ab-secreting plasma cells depends critically on CD4 T-follicular helper (TFH) cells during the germinal center reaction. Germinal center TFH cells share functional properties with circulating CXCR5(+) CD4 T cells, referred to herein as peripheral TFH (pTFH) cells. Because deficient Ab production and CD4 T-cell loss are recognized features of HIV infection, in the present study, we investigated pTFH cells in 25 HIV-infected patients on antiretroviral therapy. pTFH frequency was equivalent in patients and healthy controls (HCs), and these cells displayed a central memory phenotype. Sixteen patients and 8 HCs in this group were given a single dose of H1N1/09 influenza vaccine during the 2009 H1N1 influenza outbreak. In the vaccine responders (n = 8) and HCs, pTFH cells underwent expansion with increased IL-21 and CXCL13 secretion in H1N1-stimulated PBMC culture supernatants at week 4 (T2). These changes were not seen in vaccine nonresponders (n = 8). In coculture experiments, sorted pTFH cells supported HIN1-stimulated IgG production by autologous B cells only in vaccine responders. At T2, frequencies of pTFH were correlated with memory B cells, serum H1N1 Ab titers, and Ag-induced IL-21 secretion. Characterization of pTFH cells may provide additional insight into cellular determinants of vaccine-induced Ab response, which may have relevance for vaccine design. (Blood. 2012;120(5):985-993)