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J Immunol . Pneumonia Severity and Phase Linked to Virus-Specific T Cell Responses with Distinct Immune Checkpoints during pH1N1 Infection

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  • J Immunol . Pneumonia Severity and Phase Linked to Virus-Specific T Cell Responses with Distinct Immune Checkpoints during pH1N1 Infection


    J Immunol


    . 2022 Apr 13;ji2101021.
    doi: 10.4049/jimmunol.2101021. Online ahead of print.
    Pneumonia Severity and Phase Linked to Virus-Specific T Cell Responses with Distinct Immune Checkpoints during pH1N1 Infection


    Hui Li 1 , Min Zhao 2 3 , Hangjie Zhang 4 , Chuansong Quan 4 , Dannie Zhang 4 , Yingmei Liu 1 , Meng Liu 5 , Chunxue Xue 5 , Shuguang Tan 2 , Yaxin Guo 4 , Yingze Zhao 4 , Guizhen Wu 4 , George F Gao 6 3 4 , Bin Cao 7 5 8 , William J Liu 9 10



    Affiliations

    Abstract

    The detailed features and the longitudinal variation of influenza-specific T cell responses within naturally infected patients and the relationship with disease severity remain uncertain. 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 ± 3 d after onset of illness, effector CD8+ T cells (CD45RA+CCR7-) with high expression of inhibitory immune receptor CD200R dominated the specific T cell responses. However, at 21 ± 3 d after onset of illness, effector memory CD4+ T cells (CD45RA-CCR7-) 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.


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