Adolescent BCG revaccination induces a phenotypic shift in CD4 + T cell responses to Mycobacterium tuberculosis.
One B DintweLamar B FlemingValentin VoilletJohn P McNevinAaron SeeseAnneta NaidooSaleha OmarjeeLinda Gail BekkerJames G KublinStephen C De RosaEvan William NewellAndrew-Fiore GartlandErica Andersen-NissenM Juliana McElrathPublished in: Nature communications (2024)
A recent clinical trial demonstrated that Bacille Calmette-Guérin (BCG) revaccination of adolescents reduced the risk of sustained infection with Mycobacterium tuberculosis (M.tb). In a companion phase 1b trial, HVTN 602/Aeras A-042, we characterize in-depth the cellular responses to BCG revaccination or to a H4:IC31 vaccine boost to identify T cell subsets that could be responsible for the protection observed. High-dimensional clustering analysis of cells profiled using a 26-color flow cytometric panel show marked increases in five effector memory CD4 + T cell subpopulations (T EM ) after BCG revaccination, two of which are highly polyfunctional. CITE-Seq single-cell analysis shows that the activated subsets include an abundant cluster of Th1 cells with migratory potential. Additionally, a small cluster of Th17 T EM cells induced by BCG revaccination expresses high levels of CD103; these may represent recirculating tissue-resident memory cells that could provide pulmonary immune protection. Together, these results identify unique populations of CD4 + T cells with potential to be immune correlates of protection conferred by BCG revaccination.
Keyphrases
- mycobacterium tuberculosis
- induced apoptosis
- single cell
- cell cycle arrest
- clinical trial
- young adults
- rna seq
- endoplasmic reticulum stress
- physical activity
- cell death
- mental health
- signaling pathway
- randomized controlled trial
- study protocol
- pulmonary hypertension
- regulatory t cells
- dendritic cells
- working memory
- gene expression
- risk assessment
- phase iii
- cell proliferation
- peripheral blood
- climate change
- high throughput
- phase ii