Antigen Availability Shapes T Cell Differentiation and Function during Tuberculosis.

Autor:	Moguche AO; Center for Infectious Disease Research (CIDR), Seattle, WA 98109, USA; Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA., Musvosvi M; South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town, Cape Town 7925, South Africa; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa., Penn-Nicholson A; South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town, Cape Town 7925, South Africa; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa., Plumlee CR; Center for Infectious Disease Research (CIDR), Seattle, WA 98109, USA., Mearns H; South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town, Cape Town 7925, South Africa; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa., Geldenhuys H; South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town, Cape Town 7925, South Africa; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa., Smit E; South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town, Cape Town 7925, South Africa; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa., Abrahams D; South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town, Cape Town 7925, South Africa; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa., Rozot V; South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town, Cape Town 7925, South Africa; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa., Dintwe O; South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town, Cape Town 7925, South Africa; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa., Hoff ST; Statens Serum Institut (SSI), 2300 Copenhagen, Denmark., Kromann I; Statens Serum Institut (SSI), 2300 Copenhagen, Denmark., Ruhwald M; Statens Serum Institut (SSI), 2300 Copenhagen, Denmark., Bang P; Statens Serum Institut (SSI), 2300 Copenhagen, Denmark., Larson RP; Center for Infectious Disease Research (CIDR), Seattle, WA 98109, USA., Shafiani S; Center for Infectious Disease Research (CIDR), Seattle, WA 98109, USA., Ma S; Center for Infectious Disease Research (CIDR), Seattle, WA 98109, USA., Sherman DR; Center for Infectious Disease Research (CIDR), Seattle, WA 98109, USA., Sette A; Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla 92037, USA., Lindestam Arlehamn CS; Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla 92037, USA., McKinney DM; Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla 92037, USA., Maecker H; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA., Hanekom WA; South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town, Cape Town 7925, South Africa; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa., Hatherill M; South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town, Cape Town 7925, South Africa; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa., Andersen P; Statens Serum Institut (SSI), 2300 Copenhagen, Denmark., Scriba TJ; South African Tuberculosis Vaccine Initiative (SATVI), University of Cape Town, Cape Town 7925, South Africa; Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Cape Town 7925, South Africa; Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa. Electronic address: thomas.scriba@uct.ac.za., Urdahl KB; Center for Infectious Disease Research (CIDR), Seattle, WA 98109, USA; Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA. Electronic address: kevin.urdahl@cidresearch.org.
Jazyk:	angličtina
Zdroj:	Cell host & microbe [Cell Host Microbe] 2017 Jun 14; Vol. 21 (6), pp. 695-706.e5.
DOI:	10.1016/j.chom.2017.05.012
Abstrakt:	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. (Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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