1. Systematic Examination of Antigen-Specific Recall T Cell Responses to SARS-CoV-2 versus Influenza Virus Reveals a Distinct Inflammatory Profile.
- Author
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Law JC, Koh WH, Budylowski P, Lin J, Yue F, Abe KT, Rathod B, Girard M, Li Z, Rini JM, Mubareka S, McGeer A, Chan AK, Gingras AC, Watts TH, and Ostrowski MA
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Antigens, Viral immunology, CD4-Positive T-Lymphocytes immunology, Inflammation immunology, Orthomyxoviridae immunology, SARS-CoV-2 immunology
- Abstract
There is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. In this study, we investigated human 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 and compared them with influenza-specific memory responses from the same donors. All subjects showed SARS-CoV-2-specific T cell responses to at least one Ag. Both SARS-CoV-2-specific and influenza-specific CD4
+ T cell responses were predominantly of the central memory phenotype; however SARS-CoV-2-specific CD4+ T cells exhibited a lower IFN-γ to TNF ratio compared with influenza-specific memory responses from 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. Most SARS-CoV-2-convalescent subjects also produced IFN-γ in response to seasonal OC43 S protein. We observed granzyme B+ /IFN-γ+ , CD4+ , and CD8+ proliferative responses to peptide pools in most individuals, with CD4+ T cell responses predominating over CD8+ T cell responses. Peripheral T follicular helper (pTfh) responses to S or N strongly correlated with serum neutralization assays as well as receptor binding domain-specific IgA; however, the frequency of pTfh responses to SARS-CoV-2 was lower than the frequency of pTfh responses to influenza virus. Overall, T cell responses to SARS-CoV-2 are robust; however, CD4+ Th1 responses predominate over CD8+ T cell responses, have a more inflammatory profile, and have a weaker pTfh response than the response to influenza virus within the same donors, potentially contributing to COVID-19 disease., (Copyright © 2020 by The American Association of Immunologists, Inc.)- Published
- 2021
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