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In this study, we characterized the longitudinal influenza-specific CD4+ and CD8+ T cell responses, T cell activation, and migration-related cytokine\/chemokine secretion in pH1N1-infected patients with or without viral pneumonia with human PBMCs. Both the influenza-specific CD4+ and CD8+ T cells presented higher responses in patients with severe infection than in mild ones, but with distinct longitudinal variations, phenotypes of memory markers, and immune checkpoints. At 7 \u00b1 3 d after onset of illness, effector CD8+ T cells (CD45RA+CCR7\u2212) with high expression of inhibitory immune receptor CD200R dominated the specific T cell responses. However, at 21 \u00b1 3 d after onset of illness, effector memory CD4+ T cells (CD45RA\u2212CCR7\u2212) with high expression of PD1, CTLA4, and LAG3 were higher among the patients with severe disease. The specific T cell magnitude, T cell activation, and migration-related cytokines\/chemokines possessed a strong connection with disease severity. Our findings illuminate the distinct characteristics of immune system activation during dynamic disease phases and its correlation with lung injury of pH1N1 patients.<\/jats:p>","DOI":"10.4049\/jimmunol.2101021","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T18:01:05Z","timestamp":1649872865000},"page":"2154-2162","source":"Crossref","is-referenced-by-count":0,"title":["Pneumonia Severity and Phase Linked to Virus-Specific T Cell Responses with Distinct Immune Checkpoints during pH1N1 Infection"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6300-2455","authenticated-orcid":false,"given":"Hui","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Laboratory of Clinical Microbiology and Infectious Diseases, China-Japan Friendship Hospital , Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhao","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hangjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuansong","family":"Quan","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , 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Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunxue","family":"Xue","sequence":"additional","affiliation":[{"name":"Clinical Center for Pulmonary Infections, Capital Medical University , Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuguang","family":"Tan","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4690-8212","authenticated-orcid":false,"given":"Yaxin","family":"Guo","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingze","family":"Zhao","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guizhen","family":"Wu","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3869-615X","authenticated-orcid":false,"given":"George F","family":"Gao","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing,","place":["China"]},{"name":"NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Laboratory of Clinical Microbiology and Infectious Diseases, China-Japan Friendship Hospital , Beijing,","place":["China"]},{"name":"Clinical Center for Pulmonary Infections, Capital Medical University , Beijing,","place":["China"]},{"name":"Tsinghua University\u2013Peking University Joint Center for Life Sciences , Beijing,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9388-3671","authenticated-orcid":false,"given":"William 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