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Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842032/ https://www.ncbi.nlm.nih.gov/pubmed/35149285 http://dx.doi.org/10.1016/j.ebiom.2022.103839 |
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author | 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 |
author_facet | 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 |
author_sort | Gela, Anele |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8842032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-88420322022-02-22 Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies 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 EBioMedicine Articles 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. Elsevier 2022-02-08 /pmc/articles/PMC8842032/ /pubmed/35149285 http://dx.doi.org/10.1016/j.ebiom.2022.103839 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Articles 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 Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies |
title | Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies |
title_full | Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies |
title_fullStr | Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies |
title_full_unstemmed | Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies |
title_short | Effects of BCG vaccination on donor unrestricted T cells in two prospective cohort studies |
title_sort | effects of bcg vaccination on donor unrestricted t cells in two prospective cohort studies |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8842032/ https://www.ncbi.nlm.nih.gov/pubmed/35149285 http://dx.doi.org/10.1016/j.ebiom.2022.103839 |
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