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
1 Department of Infectious Disease Informatics, Farr Institute of Health Informatics Research.
2 Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
Am J Respir Crit Care Med. 2015 Jun 15;191(12):1422-31. doi: 10.1164/rccm.201411-1988OC.
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.
To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza.
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.
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.
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.
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。
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。
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。
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。
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。
