Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza
Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza
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DOI：
10.1164/rccm.201411-1988oc
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发表时间：
2015-06-15
影响因子：
24.7
通讯作者：
McMichael, Andrew J.
中科院分区：
文献类型：
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作者：
Hayward, Andrew C.;Wang, Lili;McMichael, Andrew J.
理由：大部分流感感染是无症状的。动物和人类的挑战研究和观察性研究表明，T细胞可以保护感染者免受疾病的侵害，但T细胞免疫在人群水平上的影响尚不清楚。目的：研究针对高度保守的内部流感蛋白的天然预先存在的T细胞应答是否可以提供针对大流行性流感和季节性流感的交叉保护性免疫。方法：我们在2006年至2010年的季节性和大流行期间对人群队列中的甲型H3 N2流感病毒特异性T细胞进行了定量。随访包括配对血清学、症状报告和有症状病例的聚合酶链反应（PCR）调查。测量和主要结果：共有1，414名未接种疫苗的个体进行了基线T细胞测量（1，703名参与者观察集）。在缺乏A（H1N1）pdm 09抗体的参与者中，对A（H3 N2）病毒核蛋白（NP）的T细胞应答占主导地位，并与A（H1N1）pdm 09 NP发生强烈交叉反应（P < 0.001）。配对的季前赛和季后赛血清（1,431组）的比较显示，205（14%）有感染的证据，基于四倍的流感抗体滴度上升。暴露于病毒前NP特异性T细胞的存在与症状较少的PCR阳性甲型流感相关（在大流行[P = 0.047]和季节性[P = 0.049]期间，总体校正比值比为0.27; 95%置信区间为0.11-0.68; P = 0.005）。保护作用不依赖于基线抗体。流感特异性T细胞反应检测到43%，表明大量的人口impacts.Conclusions：自然发生的交叉保护性T细胞免疫保护对症状性PCR证实的疾病的感染证据，并有助于解释为什么许多感染不引起症状。刺激T细胞的疫苗可以提供重要的交叉保护性免疫。
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 postseason 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.