Abstract
SummaryBackgroundNon-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.MethodsWe 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.FindingsBCG (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.InterpretationOur 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.FundingAeras, the National Institutes of Health, and the Bill and Melinda Gates Foundation.
Highlights
IntroductionBacillus Calmette-Guerin (BCG), the only licensed tuberculosis vaccine, provides variable protection against tuberculosis, the deadliest disease caused by a single infectious agent
Current approaches to develop vaccines against tuberculosis (TB), one of the top 10 causes of death globally, are based primarily on the induction of conventional, www.thelancet.com Vol 76 Month February, 2022Research in ContextEvidence before this studyBacillus Calmette-Guerin (BCG), the only licensed tuberculosis vaccine, provides variable protection against tuberculosis, the deadliest disease caused by a single infectious agent
The near-unrestricted nature of donor-unrestricted T (DURT) cell antigen recognition is of particular interest for vaccine development, and we sought to define the roles of DURT cells, including MR1restricted MAIT cells, CD1b-restricted glucose monomycolate (GMM)-specific T cells, CD1d-restricted NKT cells, and gd T cells, in vaccination against Mycobacterium tuberculosis
Summary
Bacillus Calmette-Guerin (BCG), the only licensed tuberculosis vaccine, provides variable protection against tuberculosis, the deadliest disease caused by a single infectious agent. Evidence from non-human primates and human studies suggest that DURT cells are activated during natural infection with Mycobacterium tuberculosis, providing a rationale to investigate if BCG vaccination can modulate these T cell populations in humans. We aimed to determine if BCG vaccination modulates peripheral blood frequencies, activation and expression of memory markers of MR1-restricted MAIT cells, CD1brestricted glucose monomycolate (GMM)-specific T cells, CD1d-restricted NKT cells, and gd T cells. Our findings show that neonatal BCG vaccination was associated with an increase in gd T cells as well as a novel subset of BCG-reactive IFN-g-producing CD26+CD161+TRAV1À2 À T cells that express CD4. BCG (re)vaccination did not modulate the other three DURT cell subsets
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