Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies

Anele Gela; Melissa Murphy; Miguel Rodo; Kate Hadley; Willem A. Hanekom; W.Henry Boom; John L. Johnson; Daniel F. Hoft; Simone A. Joosten; Tom H.M. Ottenhoff; Sara Suliman; D.Branch Moody; David M. Lewinsohn; Mark Hatherill; Chetan Seshadri; Elisa Nemes; Thomas J. Scriba; Libby Briel; Hellen Veldtsman; Nondumiso Khomba; Bernadette Pienaar; Hadn Africa; Marcia Steyn

EBioMedicine (Feb 2022)

Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies

Anele Gela,
Melissa Murphy,
Miguel Rodo,
Kate Hadley,
Willem A. Hanekom,
W.Henry Boom,
John L. Johnson,
Daniel F. Hoft,
Simone A. Joosten,
Tom H.M. Ottenhoff,
Sara Suliman,
D.Branch Moody,
David M. Lewinsohn,
Mark Hatherill,
Chetan Seshadri,
Elisa Nemes,
Thomas J. Scriba,
Libby Briel,
Hellen Veldtsman,
Nondumiso Khomba,
Bernadette Pienaar,
Hadn Africa,
Marcia Steyn

Affiliations

Anele Gela: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Melissa Murphy: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Miguel Rodo: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa; Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa
Kate Hadley: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Willem A. Hanekom: Africa Health Research Institute, KwaZulu-Natal, South Africa
W.Henry Boom: Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH, USA
John L. Johnson: Tuberculosis Research Unit, Department of Medicine, Case Western Reserve University and University Hospitals Cleveland Medical Center, Cleveland, OH, USA
Daniel F. Hoft: Division of Infectious Diseases, Allergy & Immunology, Edward A. Doisy Research Center, Saint Louis University School of Medicine, St. Louis, MO, USA
Simone A. Joosten: Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
Tom H.M. Ottenhoff: Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
Sara Suliman: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa; Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
D.Branch Moody: Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
David M. Lewinsohn: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Oregon Health & Science University, Portland, OR, USA
Mark Hatherill: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Chetan Seshadri: Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA
Elisa Nemes: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Thomas J. Scriba: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa; Corresponding author.
Libby Briel: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Hellen Veldtsman: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Nondumiso Khomba: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Bernadette Pienaar: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Hadn Africa: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa
Marcia Steyn: South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa

Journal volume & issue: Vol. 76
p. 103839

Abstract

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Summary: Background: Non-protein antigen classes can be presented to T cells by near-monomorphic antigen-presenting molecules such as CD1, MR1, and butyrophilin 3A1. Such T cells, referred to as donor unrestricted T (DURT) cells, typically express stereotypic T cell receptors. The near-unrestricted nature of DURT cell antigen recognition is of particular interest for vaccine development, and we sought to define the roles of DURT cells, including MR1-restricted MAIT cells, CD1b-restricted glucose monomycolate (GMM)-specific T cells, CD1d-restricted NKT cells, and γδ T cells, in vaccination against Mycobacterium tuberculosis. Methods: We compared and characterized DURT cells following primary bacille Calmette-Guerin (BCG) vaccination in a cohort of vaccinated and unvaccinated infants, as well as before and after BCG-revaccination in adults. Findings: BCG (re)vaccination did not modulate peripheral blood frequencies, T cell activation or memory profiles of MAIT cells, CD1b-restricted GMM-specific and germline-encoded mycolyl-reactive (GEM) cells or CD1d-restricted NKT cells. By contrast, primary BCG vaccination was associated with increased frequencies of γδ T cells as well as a novel subset of CD26+CD161+TRAV1-2− IFN-γ-expressing CD4+ T cells in infants. Interpretation: Our findings, that most DURT cell populations were not modulated by BCG, do not preclude a role of BCG in modulating other qualitative aspects of DURT cells. More studies are required to understand the full potential of DURT cells in new TB vaccine strategies. Funding: Aeras, the National Institutes of Health, and the Bill and Melinda Gates Foundation.

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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