Adolescent BCG revaccination induces a phenotypic shift in CD4+ T cell responses to Mycobacterium tuberculosis

Autor: One B. Dintwe, Lamar Ballweber Fleming, Valentin Voillet, John McNevin, Aaron Seese, Anneta Naidoo, Saleha Omarjee, Linda-Gail Bekker, James G. Kublin, Stephen C. De Rosa, Evan W. Newell, Andrew Fiore-Gartland, Erica Andersen-Nissen, M. Juliana McElrath
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Nature Communications, Vol 15, Iss 1, Pp 1-15 (2024)
Druh dokumentu: article
ISSN: 2041-1723
DOI: 10.1038/s41467-024-49050-1
Popis: 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+ T cell subpopulations (TEM) 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 TEM 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.
Databáze: Directory of Open Access Journals