학술논문
Functional analyses and single cell immunoprofiling uncover sex-specific differences in SARS-CoV2 immune memory development.
Document Type
Author
Eraslan B; Broad Institute of MIT and Harvard.; Brown E; Broad Institute of MIT and Harvard.; Benson M; Brigham and Women's Hospital.; Amir-Zilberstein L; Broad Institute of MIT and Harvard.; Park SM; Massachusetts General Hospital, Harvard Medical School.; Tusi B; Massachusetts General Hospital.; Pokatayev V; Broad Institute of MIT and Harvard.; Hecht C; Broad Institute of MIT and Harvard.; Pishesha N; Broad Institute of MIT and Harvard.; Phillips D; Broad Institute of MIT and Harvard.; Kim A; Brigham and Women's Hospital.; Zhang S; Broad Institute of MIT and Harvard.; Gaca A; Broad Institute of MIT and Harvard.; Ghantous F; Beth Israel Deaconess Medical Center.; Delorey T; Broad Institute at MIT.; Livny J; The Broad Institute of Massachusetts Institute of Technology and Harvard University.; Baden L; Brigham and Women's Hospital.; Rozenblatt-Rosen O; Broad Institute of Harvard and MIT.; Graham D; Broad Institute.; Regev A; Broad Institute of MIT and Harvard.; Seaman M; Beth Israel Deaconess Medical Center.; Woolley A; Brigham and Women's Hospital.; Cosimi L; Brigham and Women's Hospital.; Hung D; Broad Institute of MIT and Harvarad.; Deguine J; Broad Institute of MIT and Harvard.; Xavier R; Broad Institute of the MIT and Harvard.
Source
Country of Publication: United States NLM ID: 101768035 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: Res Sq Subsets: PubMed not MEDLINE
Subject
Language
English
Abstract
SARS-CoV-2 infection leads to a broad range of outcomes and immune responses, with the development of neutralizing antibodies generally correlated with protection against reinfection. Here, we have characterized both neutralizing activity and T cell responses in a cluster of subjects with mild disease linked to a single spreading event. Surprisingly, we observed sex-specific associations between spike- and particularly nucleoprotein-specific T cell responses and neutralization, with pro-inflammatory cytokines being linked to higher titers only in males. Using single cell immunoprofiling, which provided matched transcriptome and T-cell receptor (TCR) profiles in restimulated CD4 + and CD8 + cells from these subjects, we identified differences in type I IFN signaling that may underlie this difference in antibody generation. Finally, we also identified several TCRs associated with cytokine producing T cells. Altogether, our work maps the breadth of immunological outcomes of SARS-CoV2 infections and highlight the potential role of sex-specific feedback loops during the generation of neutralizing antibodies.
Competing Interests: Declaration of interests O.R.-R. and A.R. are co-inventors on patent applications filed by the Broad Institute for inventions related to single cell genomics. R.J.X. is co-founder and equity holder of Jnana Therapeutics. R.J.X. and A.R. are co-founders and equity holders of Celsius Therapeutics. A.R. is an equity holder in Immunitas and was an SAB member of ThermoFisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics, and Asimov. A.R. and O.R.-R. are employees of Genentech (member of the Roche Group) since August and October 2020, respectively. These companies did not provide support for this work.
Competing Interests: Declaration of interests O.R.-R. and A.R. are co-inventors on patent applications filed by the Broad Institute for inventions related to single cell genomics. R.J.X. is co-founder and equity holder of Jnana Therapeutics. R.J.X. and A.R. are co-founders and equity holders of Celsius Therapeutics. A.R. is an equity holder in Immunitas and was an SAB member of ThermoFisher Scientific, Syros Pharmaceuticals, Neogene Therapeutics, and Asimov. A.R. and O.R.-R. are employees of Genentech (member of the Roche Group) since August and October 2020, respectively. These companies did not provide support for this work.