@article{discovery1466815, month = {June}, pages = {1422--1431}, journal = {American Journal of Respiratory and Critical Care Medicine}, note = {Originally Published in: Hayward, AC; Wang, L; Goonetilleke, N; Fragaszy, EB; Bermingham, A; Copas, A; Dukes, O; (2015) Natural T Cell Mediated Protection Against Seasonal and Pandemic Influenza: Results of the Flu Watch Cohort Study. American Journal of Respiratory and Critical Care Medicine, 191 (12) pp. 1422-1431. DOI: 10.1164/rccm.201411-1988OC Copyright {\copyright} 2015 by the American Thoracic Society The final publication is available at http://dx.doi.org/10.1164/rccm.201411-1988OC.}, year = {2015}, volume = {191}, number = {12}, title = {Natural T Cell Mediated Protection Against Seasonal and Pandemic Influenza: Results of the Flu Watch Cohort Study}, keywords = {Cellular Immunity, Cohort Studies, T-Lymphocytes}, issn = {1073-449X}, abstract = {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 {\ensuremath{<}} 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.}, url = {http://dx.doi.org/10.1164/rccm.201411-1988OC}, author = {Hayward, AC and Wang, L and Goonetilleke, N and Fragaszy, EB and Bermingham, A and Copas, A and Dukes, O and Millett, ER and Nazareth, I and Nguyen-Van-Tam, JS and Watson, JM and Zambon, M and Johnson, AM and McMichael, AJ and Flu Watch Group, {}} }