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
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
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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