天然T细胞介导的针对季节性流感和大流行性流感的保护作用。流感观察队列研究结果
Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study.
作者信息
Hayward Andrew C, Wang Lili, Goonetilleke Nilu, Fragaszy Ellen B, Bermingham Alison, Copas Andrew, Dukes Oliver, Millett Elizabeth R C, Nazareth Irwin, Nguyen-Van-Tam Jonathan S, Watson John M, Zambon Maria, Johnson Anne M, McMichael Andrew J
机构信息
1 Department of Infectious Disease Informatics, Farr Institute of Health Informatics Research.
2 Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
出版信息
Am J Respir Crit Care Med. 2015 Jun 15;191(12):1422-31. doi: 10.1164/rccm.201411-1988OC.
RATIONALE
A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown.
OBJECTIVES
To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza.
METHODS
We quantified influenza A(H3N2) virus-specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases.
MEASUREMENTS AND MAIN RESULTS
A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact.
CONCLUSIONS
Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity.
原理
很大一部分流感感染是无症状的。动物和人体激发研究以及观察性研究表明，T细胞可保护感染者免于患病，但T细胞免疫在人群层面的影响尚不清楚。
目的
研究针对高度保守的流感内部蛋白的天然存在的T细胞反应是否能提供针对大流行和季节性流感的交叉保护免疫。
方法
我们在2006年至2010年的季节性和大流行期间，对一个人群队列中的甲型H3N2流感病毒特异性T细胞进行了定量分析。随访包括配对血清学检测、症状报告以及对有症状病例进行聚合酶链反应（PCR）检测。
测量指标和主要结果
共有1414名未接种疫苗的个体进行了基线T细胞检测（1703个参与者观察样本）。在缺乏甲型H1N1pdm09抗体的参与者中，对甲型H3N2病毒核蛋白（NP）的T细胞反应占主导，且与甲型H1N1pdm09NP有强烈的交叉反应（P<0.001）。配对的季前和季后血清（1431个样本）比较显示，基于流感抗体滴度四倍升高，有205例（14%）有感染证据。接触病毒前NP特异性T细胞的存在与症状较轻的PCR阳性甲型流感相关（总体调整优势比为0.27；95%置信区间为0.11-0.68；P=0.005，在大流行期间[P=0.047]和季节性流行期间[P=0.049]）。这种保护作用与基线抗体无关。在43%的人群中检测到了流感特异性T细胞反应，表明其对人群有重大影响。
结论
天然存在的交叉保护性T细胞免疫可保护有感染证据的人免受症状性PCR确诊疾病的侵害，并有助于解释为什么许多感染不会引起症状。刺激T细胞的疫苗可能提供重要的交叉保护免疫。
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