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- Title
Heterologous vaccination against human tuberculosis modulates antigen-specific CD4<sup>+</sup> T-cell function.
- Authors
Dintwe, One B.; Day, Cheryl L.; Smit, Erica; Nemes, Elisa; Gray, Clive; Tameris, Michele; McShane, Helen; Mahomed, Hassan; Hanekom, Willem A.; Scriba, Thomas J.
- Abstract
Heterologous prime-boost strategies hold promise for vaccination against tuberculosis. However, the T-cell characteristics required for protection are not known. We proposed that boost vaccines should induce long-lived functional and phenotypic changes to T cells primed by Bacille Calmette Guerin (BCG) and/or natural exposure to mycobacteria. We characterized changes among specific CD4+ T cells after vaccination with the MVA85 A vaccine in adults, adolescents, and children. CD4+ T cells identified with Ag85 A peptide-bearing HLA class II tetramers were characterized by flow cytometry. We also measured proliferative potential and cytokine expression of Ag85 A-specific CD4+ T cells. During the effector phase, MVA85 A-induced specific CD4+ T cells coexpressed IFN-γ and IL-2, skin homing integrins, and the activation marker CD38. This was followed by contraction and a transition to predominantly IL-2-expressing, CD45 RA− CCR7+ CD27+ or CD45 RA+ CCR7+ CD27+ specific CD4+ T cells. These surface phenotypes were similar to Ag85 A-specific T cells prior to MVA85 A. However, functional differences were observed postvaccination: specific proliferative capacity was markedly higher after 6-12 months than before vaccination. Our data suggest that MVA85 A vaccination may modulate Ag85 A-specific CD4+ T-cell function, resulting in greater recall potential. Importantly, surface phenotypes commonly used as proxies for memory T-cell function did not associate with functional effects of vaccination.
- Publication
European Journal of Immunology, 2013, Vol 43, Issue 9, p2409
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201343454