期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 191, 期 12, 页码 1422-1431出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.201411-1988OC
关键词
cellular immunity; T lymphocytes; cohort studies
资金
- Farr Institute of Health Informatics Research, London
- Medical Research Council
- Arthritis Research UK
- British Heart Foundation
- Cancer Research UK
- Economic and Social Research Council
- Engineering and Physical Sciences Research Council
- National Institute of Health Research
- National Institute for Social Care and Health Research (Welsh Assembly Government)
- Chief Scientist Office (Scottish Government Health Directorates)
- Wellcome Trust [MR/K006584/1]
- National Institute for Health Research Methods fellowship
- MRC [G0600511, G0800767, MC_U122785833] Funding Source: UKRI
- Medical Research Council [MC_U122785833, G0600511, MR/K006584/1, G0800767] Funding Source: researchfish
- National Institute for Health Research [NIHR-RMFI-2013-04-016-101, NF-SI-0513-10078] Funding Source: researchfish
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.
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