Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans
Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans
复制标题
血液滤泡辅助性 T 细胞亚群的早期上升和基线免疫作为人类对疫苗接种的持续晚期功能性抗体反应的预测因子
作者：
F. Spensieri;Emilio Siena;E. Borgogni;Luisanna Zedda;R. Cantisani;N. Chiappini;F. Schiavetti;D. Rosa;F. Castellino;E. Montomoli;C. Bodinham;D. Lewis;D. Medini;S. Bertholet;G. Del Giudice
CD4+T滤泡辅助细胞(TFH)是T细胞亚群中的一种，主要为B细胞提供最佳的激活和产生高亲和力抗体的帮助。我们最近证明，接种疫苗三周后，外周血中流感特异性CD4+IL-21+ICOS1+T辅助细胞(TH)细胞的扩张与禽流感H5N1保护性中和抗体的上升有关，并预测了这种中和抗体的上升。在这项研究中，健康成年人接种了普通季节性三价流感灭活疫苗(TIIV)、MF59®佐剂TIIV(ATIIV)或生理盐水安慰剂。免疫后不同时间点检测外周血中CD4+TFH1、ICOS+TFH细胞和H1N1特异性CD4+IL-21+ICOS+CXCR5+TFH和CXCR5-TH细胞亚群的频率，并与血凝抑制效价(HI)进行相关分析。所有三个CD4+T细胞亚群都随着TIIV和ATIIV的反应而扩大，并在接种后7天达到顶峰。为了证明这些TFH细胞亚群与功能性抗体效价相关，我们定义了一个替代终点指标，去相关HI(DHI)，它消除了第28天/168天和第0天HI效价之间的任何相关性，以控制先前存在的免疫对流感疫苗株的影响。第7天外周血中的总CD4+TFH1 ICOS+细胞数和H1N1特异性CD4+IL-21+ICOS+CXCR5+细胞数分别与第28天、第28天和168天的DHI滴度显著相关。总之，我们的结果表明，CD4+TFH亚群可能是疫苗诱导的长期功能免疫的有价值的生物标志物。试验注册诊所Trials.gov NCT01771367
CD4+ T follicular helper cells (TFH) have been identified as the T-cell subset specialized in providing help to B cells for optimal activation and production of high affinity antibody. We recently demonstrated that the expansion of peripheral blood influenza-specific CD4+IL-21+ICOS1+ T helper (TH) cells, three weeks after vaccination, associated with and predicted the rise of protective neutralizing antibodies to avian H5N1. In this study, healthy adults were vaccinated with plain seasonal trivalent inactivated influenza vaccine (TIIV), MF59®-adjuvanted TIIV (ATIIV), or saline placebo. Frequencies of circulating CD4+ TFH1 ICOS+ TFH cells and H1N1-specific CD4+IL-21+ICOS+ CXCR5+ TFH and CXCR5- TH cell subsets were determined at various time points after vaccination and were then correlated with hemagglutination inhibition (HI) titers. All three CD4+ T cell subsets expanded in response to TIIV and ATIIV, and peaked 7 days after vaccination. To demonstrate that these TFH cell subsets correlated with functional antibody titers, we defined an alternative endpoint metric, decorrelated HI (DHI), which removed any correlation between day 28/day 168 and day 0 HI titers, to control for the effect of preexisting immunity to influenza vaccine strains. The numbers of total circulating CD4+ TFH1 ICOS+ cells and of H1N1-specific CD4+IL-21+ICOS+ CXCR5+, measured at day 7, were significantly associated with day 28, and day 28 and 168 DHI titers, respectively. Altogether, our results show that CD4+ TFH subsets may represent valuable biomarkers of vaccine-induced long-term functional immunity. Trial Registration ClinicalTrials.gov NCT01771367
影响因子：
20.3
作者：
Pallikkuth, Suresh;Parmigiani, Anita;Pahwa, Savita
通讯作者：
Pahwa, Savita
影响因子：
32.4
作者：
Locci M;Havenar-Daughton C;Landais E;Wu J;Kroenke MA;Arlehamn CL;Su LF;Cubas R;Davis MM;Sette A;Haddad EK;International AIDS Vaccine Initiative Protocol C Principal Investigators;Poignard P;Crotty S
通讯作者：
Crotty S