| Literature DB >> 28618268 |
Albanus O Moguche1, Munyaradzi Musvosvi2, Adam Penn-Nicholson2, Courtney R Plumlee3, Helen Mearns2, Hennie Geldenhuys2, Erica Smit2, Deborah Abrahams2, Virginie Rozot2, One Dintwe2, Søren T Hoff4, Ingrid Kromann4, Morten Ruhwald4, Peter Bang4, Ryan P Larson3, Shahin Shafiani3, Shuyi Ma3, David R Sherman3, Alessandro Sette5, Cecilia S Lindestam Arlehamn5, Denise M McKinney5, Holden Maecker6, Willem A Hanekom2, Mark Hatherill2, Peter Andersen4, Thomas J Scriba7, Kevin B Urdahl8.
Abstract
CD4 T cells are critical for protective immunity against Mycobacterium tuberculosis (Mtb), the cause of tuberculosis (TB). Yet to date, TB vaccine candidates that boost antigen-specific CD4 T cells have conferred little or no protection. Here we examined CD4 T cell responses to two leading TB vaccine antigens, ESAT-6 and Ag85B, in Mtb-infected mice and in vaccinated humans with and without underlying Mtb infection. In both species, Mtb infection drove ESAT-6-specific T cells to be more differentiated than Ag85B-specific T cells. The ability of each T cell population to control Mtb in the lungs of mice was restricted for opposite reasons: Ag85B-specific T cells were limited by reduced antigen expression during persistent infection, whereas ESAT-6-specific T cells became functionally exhausted due to chronic antigenic stimulation. Our findings suggest that different vaccination strategies will be required to optimize protection mediated by T cells recognizing antigens expressed at distinct stages of Mtb infection.Entities:
Keywords: Ag85B; CD4 T cell; ESAT-6; Mycobacterium tuberculosis; T cell differentiation; antigens; effector T cell; memory T cell; vaccines
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Year: 2017 PMID： 28618268 PMCID： PMC5533182 DOI： 10.1016/j.chom.2017.05.012
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023