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Delayed generation of functional virus-specific circulating T follicular helper cells correlates with severe COVID-19.
Yu, Meng; Charles, Afandi; Cagigi, Alberto; Christ, Wanda; Österberg, Björn; Falck-Jones, Sara; Azizmohammadi, Lida; Åhlberg, Eric; Falck-Jones, Ryan; Svensson, Julia; Nie, Mu; Warnqvist, Anna; Hellgren, Fredrika; Lenart, Klara; Arcoverde Cerveira, Rodrigo; Ols, Sebastian; Lindgren, Gustaf; Lin, Ang; Maecker, Holden; Bell, Max; Johansson, Niclas; Albert, Jan; Sundling, Christopher; Czarnewski, Paulo; Klingström, Jonas; Färnert, Anna; Loré, Karin; Smed-Sörensen, Anna.
Afiliação
  • Yu M; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Charles A; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Cagigi A; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Christ W; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
  • Österberg B; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Falck-Jones S; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Azizmohammadi L; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Åhlberg E; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Falck-Jones R; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
  • Svensson J; Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
  • Nie M; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Warnqvist A; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Hellgren F; Division of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Lenart K; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Arcoverde Cerveira R; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Ols S; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Lindgren G; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Lin A; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Maecker H; Division of Immunology and Allergy, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
  • Bell M; The Human Immune Monitoring Center, Institute of Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  • Johansson N; Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
  • Albert J; Department of Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, Sweden.
  • Sundling C; Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Czarnewski P; Department of Infectious Diseases, Karolinska University Hospital Solna, Stockholm, Sweden.
  • Klingström J; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
  • Färnert A; Clinical Microbiology, Karolinska University Hospital Solna, Stockholm, Sweden.
  • Loré K; Division of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Smed-Sörensen A; Department of Infectious Diseases, Karolinska University Hospital Solna, Stockholm, Sweden.
Nat Commun ; 14(1): 2164, 2023 04 15.
Article em En | MEDLINE | ID: mdl-37061513
Effective humoral immune responses require well-orchestrated B and T follicular helper (Tfh) cell interactions. Whether these interactions are impaired and associated with COVID-19 disease severity is unclear. Here, longitudinal blood samples across COVID-19 disease severity are analysed. We find that during acute infection SARS-CoV-2-specific circulating Tfh (cTfh) cells expand with disease severity. SARS-CoV-2-specific cTfh cell frequencies correlate with plasmablast frequencies and SARS-CoV-2 antibody titers, avidity and neutralization. Furthermore, cTfh cells but not other memory CD4 T cells, from severe patients better induce plasmablast differentiation and antibody production compared to cTfh cells from mild patients. However, virus-specific cTfh cell development is delayed in patients that display or later develop severe disease compared to those with mild disease, which correlates with delayed induction of high-avidity neutralizing antibodies. Our study suggests that impaired generation of functional virus-specific cTfh cells delays high-quality antibody production at an early stage, potentially enabling progression to severe disease.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T Auxiliares-Indutores / COVID-19 Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Linfócitos T Auxiliares-Indutores / COVID-19 Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article