Antigen Availability Shapes T Cell Differentiation and Function during Tuberculosis.

TitleAntigen Availability Shapes T Cell Differentiation and Function during Tuberculosis.
Publication TypeJournal Article
Year of Publication2017
AuthorsMoguche AO, Musvosvi M, Penn-Nicholson A, Plumlee CR, Mearns H, Geldenhuys H, Smit E, Abrahams D, Rozot V, Dintwe O, Hoff ST, Kromann I, Ruhwald M, Bang P, Larson RP, Shafiani S, Ma S, Sherman DR, Sette A, Arlehamn CSLindesta, McKinney DM, Maecker H, Hanekom WA, Hatherill M, Andersen P, Scriba TJ, Urdahl KB
JournalCell Host Microbe
Volume21
Issue6
Pagination695-706.e5
Date Published2017 Jun 14
ISSN1934-6069
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.

DOI10.1016/j.chom.2017.05.012
Alternate JournalCell Host Microbe
PubMed ID28618268
Grant ListR01 AI087915 / AI / NIAID NIH HHS / United States