A unique cytotoxic CD4 + T cell-signature defines critical COVID-19.

Autor: Baird S; Sydney Infectious Diseases Institute, Faculty of Medicine and Health The University of Sydney NSW Camperdown Australia.; School of Medical Sciences and Charles Perkins Centre The University of Sydney Camperdown NSW Australia., Ashley CL; Sydney Infectious Diseases Institute, Faculty of Medicine and Health The University of Sydney NSW Camperdown Australia.; School of Medical Sciences and Charles Perkins Centre The University of Sydney Camperdown NSW Australia., Marsh-Wakefield F; School of Medical Sciences and Charles Perkins Centre The University of Sydney Camperdown NSW Australia.; Liver Injury and Cancer Program Centenary Institute Camperdown NSW Australia.; Human Cancer and Viral Immunology Laboratory The University of Sydney Camperdown NSW Australia., Alca S; Sydney Infectious Diseases Institute, Faculty of Medicine and Health The University of Sydney NSW Camperdown Australia.; School of Medical Sciences and Charles Perkins Centre The University of Sydney Camperdown NSW Australia., Ashhurst TM; School of Medical Sciences and Charles Perkins Centre The University of Sydney Camperdown NSW Australia.; Sydney Cytometry Core Research Facility Charles Perkins Centre, Centenary Institute and The University of Sydney Camperdown NSW Australia., Ferguson AL; School of Medical Sciences and Charles Perkins Centre The University of Sydney Camperdown NSW Australia.; Liver Injury and Cancer Program Centenary Institute Camperdown NSW Australia., Lukeman H; Sydney Infectious Diseases Institute, Faculty of Medicine and Health The University of Sydney NSW Camperdown Australia.; School of Medical Sciences and Charles Perkins Centre The University of Sydney Camperdown NSW Australia., Counoupas C; Sydney Infectious Diseases Institute, Faculty of Medicine and Health The University of Sydney NSW Camperdown Australia.; School of Medical Sciences and Charles Perkins Centre The University of Sydney Camperdown NSW Australia.; Tuberculosis Research Program Centenary Institute Sydney NSW Australia., Post JJ; Prince of Wales Clinical School UNSW Sydney NSW Australia.; School of Clinical Medicine, Medicine & Health UNSW Sydney NSW Australia., Konecny P; Prince of Wales Clinical School UNSW Sydney NSW Australia.; St George Hospital Sydney NSW Australia., Bartlett A; The Kirby Institute, UNSW Sydney NSW Australia.; School of Biomedical Sciences, Medicine & Health UNSW Sydney NSW Australia.; Sydney Children's Hospital Sydney NSW Australia., Martinello M; The Kirby Institute, UNSW Sydney NSW Australia., Bull RA; The Kirby Institute, UNSW Sydney NSW Australia.; School of Biomedical Sciences, Medicine & Health UNSW Sydney NSW Australia., Lloyd A; The Kirby Institute, UNSW Sydney NSW Australia.; School of Biomedical Sciences, Medicine & Health UNSW Sydney NSW Australia., Grey A; RPA Virtual Hospital, Sydney Local Health District Sydney NSW Australia., Hutchings O; RPA Virtual Hospital, Sydney Local Health District Sydney NSW Australia., Palendira U; School of Medical Sciences and Charles Perkins Centre The University of Sydney Camperdown NSW Australia.; Liver Injury and Cancer Program Centenary Institute Camperdown NSW Australia., Britton WJ; Tuberculosis Research Program Centenary Institute Sydney NSW Australia.; Department of Clinical Immunology Royal Prince Alfred Hospital Camperdown NSW Australia., Steain M; Sydney Infectious Diseases Institute, Faculty of Medicine and Health The University of Sydney NSW Camperdown Australia.; School of Medical Sciences and Charles Perkins Centre The University of Sydney Camperdown NSW Australia., Triccas JA; Sydney Infectious Diseases Institute, Faculty of Medicine and Health The University of Sydney NSW Camperdown Australia.; School of Medical Sciences and Charles Perkins Centre The University of Sydney Camperdown NSW Australia.
Jazyk: angličtina
Zdroj: Clinical & translational immunology [Clin Transl Immunology] 2023 Aug 28; Vol. 12 (8), pp. e1463. Date of Electronic Publication: 2023 Aug 28 (Print Publication: 2023).
DOI: 10.1002/cti2.1463
Abstrakt: Objectives: SARS-CoV-2 infection causes a spectrum of clinical disease presentation, ranging from asymptomatic to fatal. While neutralising antibody (NAb) responses correlate with protection against symptomatic and severe infection, the contribution of the T-cell response to disease resolution or progression is still unclear. As newly emerging variants of concern have the capacity to partially escape NAb responses, defining the contribution of individual T-cell subsets to disease outcome is imperative to inform the development of next-generation COVID-19 vaccines.
Methods: Immunophenotyping of T-cell responses in unvaccinated individuals was performed, representing the full spectrum of COVID-19 clinical presentation. Computational and manual analyses were used to identify T-cell populations associated with distinct disease states.
Results: Critical SARS-CoV-2 infection was characterised by an increase in activated and cytotoxic CD4 + lymphocytes (CTL). These CD4 + CTLs were largely absent in asymptomatic to severe disease states. In contrast, non-critical COVID-19 was associated with high frequencies of naïve T cells and lack of activation marker expression.
Conclusion: Highly activated and cytotoxic CD4 + T-cell responses may contribute to cell-mediated host tissue damage and progression of COVID-19. Induction of these potentially detrimental T-cell responses should be considered when developing and implementing effective COVID-19 control strategies.
Competing Interests: The authors declare no conflict of interest.
(© 2023 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje