Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection

Cheleka A.M. Mpande; Virginie Rozot; Boitumelo Mosito; Munyaradzi Musvosvi; One B. Dintwe; Nicole Bilek; Mark Hatherill; Thomas J. Scriba; Elisa Nemes

EBioMedicine (Feb 2021)

Immune profiling of Mycobacterium tuberculosis-specific T cells in recent and remote infection

Cheleka A.M. Mpande,
Virginie Rozot,
Boitumelo Mosito,
Munyaradzi Musvosvi,
One B. Dintwe,
Nicole Bilek,
Mark Hatherill,
Thomas J. Scriba,
Elisa Nemes

Affiliations

Cheleka A.M. Mpande: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, South Africa
Virginie Rozot: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, South Africa
Boitumelo Mosito: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, South Africa
Munyaradzi Musvosvi: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, South Africa
One B. Dintwe: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, South Africa
Nicole Bilek: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, South Africa
Mark Hatherill: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, South Africa
Thomas J. Scriba: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, South Africa
Elisa Nemes: Corresponding author.; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine, Division of Immunology, Department of Pathology, University of Cape Town, South Africa

Journal volume & issue: Vol. 64
p. 103233

Abstract

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Background: Recent Mycobacterium tuberculosis (M.tb) infection is associated with a higher risk of progression to tuberculosis disease, compared to persistent infection after remote exposure. However, current immunodiagnostic tools fail to distinguish between recent and remote infection. We aimed to characterise the immunobiology associated with acquisition of M.tb infection and identify a biomarker that can distinguish recent from remote infection. Methods: Healthy South African adolescents were serially tested with QuantiFERON-TB Gold to define recent (QuantiFERON-TB conversion 1.5 year) infection. We characterised M.tb-specific CD4 T cell functional (IFN-γ, TNF, IL-2, CD107, CD154), memory (CD45RA, CCR7, CD27, KLRG-1) and activation (HLA-DR) profiles by flow cytometry after CFP-10/ESAT-6 peptide pool or M.tb lysate stimulation. We then assessed the diagnostic performance of immune profiles that were differentially expressed between individuals with recent or persistent QuantiFERON-TB+. Findings: CFP-10/ESAT-6-specific CD4 T cell activation but not functional or memory phenotypes distinguished between individuals with recent and persistent QuantiFERON-TB+. In response to M.tb lysate, recent QuantiFERON-TB+ individuals had lower proportions of highly differentiated IFN-γ+TNF+ CD4 T cells expressing a KLRG-1+ effector phenotype and higher proportions of early differentiated IFN-γ-TNF+IL-2+ and activated CD4 T cells compared to persistent QuantiFERON-TB+ individuals. Among all differentially expressed T cell features CFP-10/ESAT-6-specific CD4 T cell activation was the best performing diagnostic biomarker of recent infection. Interpretation: Recent M.tb infection is associated with highly activated and moderately differentiated functional M.tb-specific T cell subsets, that can be used as biomarkers to distinguish between recent and remote infection. Funding: US National Institutes of Health (NIH), Bill and Melinda Gates Foundation, South African National Research Foundation, South African Medical Research Council, and Aeras.

Published in EBioMedicine

ISSN: 2352-3964 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General)
Website: http://www.journals.elsevier.com/ebiomedicine/

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