cross-reactive t cells are involved in rapid clearance of 2009 pandemic h1n1 influenza virus in nonhuman primates可交叉反应的t细胞参与快速清除2009年甲型h1n1流感病毒在非人灵长类动物.pdf

Cross-Reactive T Cells Are Involved in Rapid Clearance of 2009 Pandemic H1N1 Influenza Virus in Nonhuman Primates 1,2 1 1 2 3 Jason T. Weinfurter , Kevin Brunner , Saverio V. Capuano III , Chengjun Li , Karl W. Broman , Yoshihiro Kawaoka2,4,5,6, Thomas C. Friedrich1,2* 1 Wisconsin National Primate Research Center, Madison, Wisconsin, United States of America, 2 Department of Pathobiological Sciences, University of Wisconsin School of Veterinary Medicine, Madison, Wisconsin, United States of America, 3 Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States of America, 4 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan, 5 Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan, 6 ERATO Infection-Induced Host Responses Project, Saitama, Japan Abstract In mouse models of influenza, T cells can confer broad protection against multiple viral subtypes when antibodies raised against a single subtype fail to do so. However, the role of T cells in protecting humans against influenza remains unclear. Here we employ a translational nonhuman primate model to show that cross-reactive T cell responses play an important role in early clearance of infection with 2009 pandemic H1N1 influenza virus (H1N1pdm). To ‘‘prime’’ cellular immunity, we first infected 5 rhesus macaques with a seasonal human H1N1 isolate. These animals made detectable cellular and antibody responses against the seasonal H1N1 isolate but had no neutralizing antibodies against H1N1pdm. Four months late