EBioMedicine · 2022
Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies.
СтатьяНазвание и аннотация: Перевод в очереди
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Gela Anele, Murphy Melissa, Rodo Miguel, Hadley Kate, Hanekom Willem A, Boom W Henry, Johnson John L, Hoft Daniel F, Joosten Simone A, Ottenhoff Tom H M, Suliman Sara, Moody D Branch, Lewinsohn David M, Hatherill Mark, Seshadri Chetan, Nemes Elisa, Scriba Thomas J, Briel Libby, Veldtsman Hellen, Khomba Nondumiso, Pienaar Bernadette, Africa Hadn, Steyn Marcia, Delayed BCG Study Team
Аннотация
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.
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.