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Systematic examination of T cell responses to SARS-CoV-2 versus influenza virus reveals distinct inflammatory profile
Jaclyn C Law; Wan Koh; Patrick Budylowski; Jonah Lin; FengYun Yue; Kento T Abe; Bhavisha Rathod; Melanie Girard; Zhijie Li; James M Rini; Samira Mubareka; Allison McGeer; Adrienne K Chan; Anne-Claude Gingras; Tania H Watts; Mario Ostrowski.
Afiliación
  • Jaclyn C Law; University of Toronto
  • Wan Koh; University of Toronto
  • Patrick Budylowski; University of Toronto
  • Jonah Lin; University of Toronto
  • FengYun Yue; Universitiy of Toronto
  • Kento T Abe; Lunenfeld-Tanenbaum Research Institute at Mt. Sinai Hospital, Sinai Health System
  • Bhavisha Rathod; Lunenfeld-Tanenbaum Research Institute at Mt. Sinai Hospital, Sinai Health System, Toronto, ON Canada
  • Melanie Girard; University of Toronto
  • Zhijie Li; University of Toronto
  • James M Rini; University of Toronto
  • Samira Mubareka; Sunnybrook Research Institute
  • Allison McGeer; Lunenfeld-Tanenbaum Research Institute at Mt. Sinai Hospital, Sinai Health System
  • Adrienne K Chan; Sunnybrook Research Institute
  • Anne-Claude Gingras; Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital; Sinai Health System
  • Tania H Watts; University of Toronto
  • Mario Ostrowski; University of Toronto
Preprint en En | PREPRINT-MEDRXIV | ID: ppmedrxiv-20183319
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-{gamma} to TNF- 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-{gamma}g+ 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.
Licencia
cc_by_nc_nd
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Prognostic_studies / Systematic_reviews Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Prognostic_studies / Systematic_reviews Idioma: En Año: 2020 Tipo del documento: Preprint