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
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.
