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Cell Host Microbe. 2017 Jun 14;21(6):695-706.e5. doi: 10.1016/j.chom.2017.05.012.

Antigen Availability Shapes T Cell Differentiation and Function during Tuberculosis.

Author information

1
Center for Infectious Disease Research (CIDR), Seattle, WA 98109, USA; Department of Immunology, University of Washington School of Medicine, Seattle, WA 98195, USA.
2
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.
3
Center for Infectious Disease Research (CIDR), Seattle, WA 98109, USA.
4
Statens Serum Institut (SSI), 2300 Copenhagen, Denmark.
5
Department of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla 92037, USA.
6
Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA 94305, USA.
7
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.
8
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.

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.

KEYWORDS:

Ag85B; CD4 T cell; ESAT-6; Mycobacterium tuberculosis; T cell differentiation; antigens; effector T cell; memory T cell; vaccines

PMID:
28618268
PMCID:
PMC5533182
DOI:
10.1016/j.chom.2017.05.012
[Indexed for MEDLINE]
Free PMC Article

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