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Gela, A.; Murphy, M.; Rodo, M.; Hadley, K.; Hanekom, W.A.; Boom, W.H.; ... ; Delayed BCG Study Team (2022)

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

Article / Letter to editor
Background: Non-protein antigen classes can be presented to T cells by near-monomorphic antigen-presenting molecules such as CDI, MRI, and butyrophilin 3AI. 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 MRI-restricted MAIT cells, CDth-restricted glucose monomycolate (GMM)-specific T cells, CDth-restricted NKT cells, and gamma delta 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, CDth...Show moreBackground: Non-protein antigen classes can be presented to T cells by near-monomorphic antigen-presenting molecules such as CDI, MRI, and butyrophilin 3AI. 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 MRI-restricted MAIT cells, CDth-restricted glucose monomycolate (GMM)-specific T cells, CDth-restricted NKT cells, and gamma delta 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, CDth-restricted GMM-specific and germline-encoded mycolyl-reactive (GEM) cells or CDId-restricted NKT cells. By contrast, primary BCG vaccination was associated with increased frequencies of gamma delta T cells as well as a novel subset of CD26(+)CDI6I(+)TRAVI-2(-) IFN-gamma-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. Copyright (C) 2022 The Authors. Published by Elsevier B.V.Show less
BCG
Tuberculosis
Vaccination
Unconventional T cells
Memory
All authors
Gela, A.; Murphy, M.; Rodo, M.; Hadley, K.; Hanekom, W.A.; Boom, W.H.; Johnson, J.L.; Hoft, D.F.; Joosten, S.A.; Ottenhoff, T.H.M.; Suliman, S.; Moody, D.B.; Lewinsohn, D.M.; Hatherill, M.; Seshadri, C.; Nemes, E.; Scriba, T.J.; Briel, L.; Veldtsman, H.; Khomba, N.; Pienaar, B.; Africa, H.; Steyn, M.; Delayed BCG Study Team
Date
2022-02-01
Journal
EBioMedicine
Volume
76
DOI
doi:10.1016/j.ebiom.2022.103839