Adolescent BCG revaccination induces a phenotypic shift in CD4<sup>+</sup> T cell responses to Mycobacterium tuberculosis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38890283.
- Also identified by DOI 10.1038/s41467-024-49050-1 and PMC identifier 11189459.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sup>+</sup> T cell subpopulations (T<sub>EM</sub>) 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<sub>EM</sub> 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<sup>+</sup> T cells with potential to be immune correlates of protection conferred by BCG revaccination.
Medical subject headings
- Mycobacterium tuberculosis
- CD4-Positive T-Lymphocytes
- BCG Vaccine