T Cells Specific for a Mycobacterial Glycolipid Expand after Intravenous Bacillus Calmette–Guérin Vaccination

Abstract

Intradermal vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) protects infants from disseminated tuberculosis, and i.v. BCG protects nonhuman primates (NHP) against pulmonary and extrapulmonary tuberculosis. In humans and NHP, protection is thought to be mediated by T cells, which typically recognize bacterial peptide Ags bound to MHC proteins. However, during vertebrate evolution, T cells acquired the capacity to recognize lipid Ags bound to CD1a, CD1b, and CD1c proteins expressed on APCs. It is unknown whether BCG induces T cell immunity to mycobacterial lipids and whether CD1-restricted T cells are resident in the lung. In this study, we developed and validated Macaca mulatta (Mamu) CD1b and CD1c tetramers to probe ex vivo phenotypes and functions of T cells specific for glucose monomycolate (GMM), an immunodominant mycobacterial lipid Ag. We discovered that CD1b and CD1c present GMM to T cells in both humans and NHP. We show that GMM-specific T cells are expanded in rhesus macaque blood 4 wk after i.v. BCG, which has been shown to protect NHP with near-sterilizing efficacy upon M. tuberculosis challenge. After vaccination, these T cells are detected at high frequency within bronchoalveolar fluid and express CD69 and CD103, markers associated with resident memory T cells. Thus, our data expand the repertoire of T cells known to be induced by whole cell mycobacterial vaccines, such as BCG, and show that lipid Ag-specific T cells are resident in the lungs, where they may contribute to protective immunity.

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

“… 1 We characterized frequencies, phenotypic and functional characteristics of DURT cell populations in the peripheral blood following BCG vaccination to explore their potential as possible immunological targets for TB vaccination. Evidence that γδ T cells, MAIT, NKT and GEM T cells can respond to mycobacteria 15 , 43 , 44 , 45 , 46 , 47 provides a strong rationale to investigate if BCG vaccination can modulate these T cell populations.…”

“…[8][9][10] A recent study in non-human primates also reported that glucose monomycolate (GMM)-specific CD1c-restricted T cells expanded after intravenous bacille Calmette-Guerin (BCG) administration. 11 Vaccination of guinea pigs with mycobacterial lipids formulated in liposomes was also associated with a reduction in the number of lesions, severity of pathology, and reduction of bacterial load upon challenge with M.tb. 12 Activation of MR1-restricted MAIT cells, which recognize vitamin B metabolites presented by the monomorphic MHC class 1-related molecule (MR1), has been shown in response to a variety of bacteria including BCG, Francisella tularensis, Klebsiella pneumonia, and M. tb.…”

“… 8 , 9 , 10 A recent study in non-human primates also reported that glucose monomycolate (GMM)-specific CD1c-restricted T cells expanded after intravenous bacille Calmette-Guerin (BCG) administration. 11 Vaccination of guinea pigs with mycobacterial lipids formulated in liposomes was also associated with a reduction in the number of lesions, severity of pathology, and reduction of bacterial load upon challenge with M.tb. 12 …”

Active Covid-19 infection and transmission after the first dose of the BNT162b2 mRNA vaccination in Saudi Arabia: A case report

“…The concept of vaccination is dependent on eliciting an adaptive immune response, B and T cells, from which memory cells will develop and provide long-lasting immunity. Although an immune response can happen as early as within the first week, long-lasting immunity can take up to 4 weeks to develop [ 2 , 3 ]. The BNT162b2 vaccine was shown to elicit an effective humoral (antibody-mediated) and cellular (T-cell-mediated) responses a week after the booster dose.…”

A simple assay to quantify mycobacterial lipid antigen-specific T cell receptors in human tissues and blood

“…For example, some T cells that recognize mycolic acid derivatives, which are abundant in the mycobacterial cell wall, always express TCR-ɑ chains containing a rearrangement of the TCR-ɑ variable (TRAV)-1-2 and TCR-ɑ joining (TRAJ) 9 genes [ 10 ]. These cells are known as germline encoded mycolyl-reactive (GEM) T cells and are detectable at high-frequency in the blood of humans with latent and active TB as well as non-human primates after vaccination with BCG [ 11 , 12 ]. Because the GEM TCR-ɑ sequence is conserved across genetically unrelated individuals, quantitative detection should be possible without the need for deep-sequencing or advanced computational methods.…”