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首页|Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile

Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile

Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile

来源:medRxiv_logomedRxiv
英文摘要

Abstract There is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. Here we investigated T cell recall responses to fully glycosylated Spike trimer, recombinant N protein as well as to S, N, M and E peptide pools in the early convalescent phase. All subjects showed SARS-CoV-2-specific T cell responses to at least one antigen. SARS-CoV-2-specific CD4+ T cells were primarily of the central memory phenotype and exhibited a lower IFN-γ to TNF-α ratio compared to influenza-specific responses of the same donors, independent of disease severity. SARS-CoV-2-specific T cells were less multifunctional than influenza-specific T cells, particularly in severe cases, potentially suggesting exhaustion. High IL-10 production was noted in response to N protein, possibly contributing to immunosuppression, with potential implications for vaccine design. We observed granzyme B+/IFN-γg+ CD4+ and CD8+ proliferative responses to peptide pools in most individuals, with CD4+ responses predominating over CD8+ responses. Peripheral T follicular helper responses to S or N strongly correlated with serum neutralization assays as well as RBD-specific IgA. Overall, T cell responses to SARS-CoV-2 are robust, however, CD4+ Th1 responses predominate over CD8+ responses and are more inflammatory with a weaker Tfh response than influenza-specific CD4+ responses, potentially contributing to COVID-19 disease.

Rathod Bhavisha、Girard Melanie、Li Zhijie、Chan Adrienne K.、Law Jaclyn C.、Budylowski Patrick、Abe Kento T.、Mubareka Samira、Koh Wan Hon、Lin Jonah、McGeer Allison、Ostrowski Mario、Watts Tania H.、Yue FengYun、Gingras Anne-Claude、Rini James M.

Lunenfeld-Tanenbaum Research Institute at Mt. Sinai Hospital, Sinai Health SystemDepartment of Immunology, University of TorontoDepartment of Molecular Genetics, University of TorontoSunnybrook Research Institute||Division of Infectious diseases, Department of Medicine, University of Toronto||Keenan Research Centre for Biomedical Science of St. Michael?ˉs Hospital, UnityHealthDepartment of Immunology, University of TorontoDepartment of Medicine, University of Toronto||Institute of Medical Science, University of TorontoLunenfeld-Tanenbaum Research Institute at Mt. Sinai Hospital, Sinai Health System||Department of Molecular Genetics, University of TorontoSunnybrook Research Institute||Department of Laboratory Medicine and Pathobiology, University of TorontoDepartment of Immunology, University of Toronto||Department of Medicine, University of TorontoDepartment of Immunology, University of TorontoLunenfeld-Tanenbaum Research Institute at Mt. Sinai Hospital, Sinai Health System||Department of Laboratory Medicine and Pathobiology, University of TorontoDepartment of Immunology, University of Toronto||Department of Medicine, University of Toronto||Keenan Research Centre for Biomedical Science of St. Michael?ˉs Hospital, UnityHealthDepartment of Immunology, University of TorontoDepartment of Medicine, University of TorontoLunenfeld-Tanenbaum Research Institute at Mt. Sinai Hospital, Sinai Health System||Department of Molecular Genetics, University of TorontoDepartment of Molecular Genetics, University of Toronto

10.1101/2020.08.27.20183319

医学研究方法基础医学

Rathod Bhavisha,Girard Melanie,Li Zhijie,Chan Adrienne K.,Law Jaclyn C.,Budylowski Patrick,Abe Kento T.,Mubareka Samira,Koh Wan Hon,Lin Jonah,McGeer Allison,Ostrowski Mario,Watts Tania H.,Yue FengYun,Gingras Anne-Claude,Rini James M..Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile[EB/OL].(2025-03-28)[2025-04-29].https://www.medrxiv.org/content/10.1101/2020.08.27.20183319.点此复制

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