Publication date: 14 June 2017
Source:Cell Host & Microbe, Volume 21, Issue 6
Author(s): Albanus O. Moguche, Munyaradzi Musvosvi, Adam Penn-Nicholson, Courtney R. Plumlee, Helen Mearns, Hennie Geldenhuys, Erica Smit, Deborah Abrahams, Virginie Rozot, One Dintwe, Søren T. Hoff, Ingrid Kromann, Morten Ruhwald, Peter Bang, Ryan P. Larson, Shahin Shafiani, Shuyi Ma, David R. Sherman, Alessandro Sette, Cecilia S. Lindestam Arlehamn, Denise M. McKinney, Holden Maecker, Willem A. Hanekom, Mark Hatherill, Peter Andersen, Thomas J. Scriba, Kevin B. Urdahl
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.
Graphical abstract
Teaser
Moguche and Musvosvi et al. show that two leading Mycobacterium tuberculosis vaccine antigens, Ag85B and ESAT-6, are differentially expressed during infection. As a result, CD4 T cells recognizing these antigens exhibit distinct patterns of differentiation, and their capacities to mediate protective immunity are restricted in different ways.http://ift.tt/2tn52K8
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