TCR Affinity Controls the Dynamics but Not the Functional Specification of the Antimycobacterial CD4 + T Cell Response.

Autor:	Bhattacharyya ND; Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia.; Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia., Counoupas C; Microbial Pathogenesis and Immunity Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia.; Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia., Daniel L; Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia.; Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia., Zhang G; Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia.; Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.; National Clinical Research Center for Infectious Diseases, Guangdong Key Laboratory of Emerging Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China., Cook SJ; Immune Imaging Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia., Cootes TA; Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia.; Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia., Stifter SA; Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia.; Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia., Bowen DG; Liver Immunology Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.; AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; and., Triccas JA; Microbial Pathogenesis and Immunity Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia.; Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.; Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, New South Wales, Australia., Bertolino P; Liver Immunology Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.; AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; and., Britton WJ; Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia., Feng CG; Immunology and Host Defense Group, Department of Infectious Diseases and Immunology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, New South Wales, Australia; carl.feng@sydney.edu.au.; Tuberculosis Research Program, Centenary Institute, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.; Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, New South Wales, Australia.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2021 Jun 15; Vol. 206 (12), pp. 2875-2887. Date of Electronic Publication: 2021 May 28.
DOI:	10.4049/jimmunol.2001271
Abstrakt:	The quality of T cell responses depends on the lymphocytes' ability to undergo clonal expansion, acquire effector functions, and traffic to the site of infection. Although TCR signal strength is thought to dominantly shape the T cell response, by using TCR transgenic CD4 + T cells with different peptide:MHC binding affinity, we reveal that TCR affinity does not control Th1 effector function acquisition or the functional output of individual effectors following mycobacterial infection in mice. Rather, TCR affinity calibrates the rate of cell division to synchronize the distinct processes of T cell proliferation, differentiation, and trafficking. By timing cell division-dependent IL-12R expression, TCR affinity controls when T cells become receptive to Th1-imprinting IL-12 signals, determining the emergence and magnitude of the Th1 effector pool. These findings reveal a distinct yet cooperative role for IL-12 and TCR binding affinity in Th1 differentiation and suggest that the temporal activation of clones with different TCR affinity is a major strategy to coordinate immune surveillance against persistent pathogens. (Copyright © 2021 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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