A mycolic acid-specific CD1-restricted T cell population contributes to acute and memory immune responses in human tuberculosis infection.

Montamat-Sicotte, DJ, Millington, KA, Willcox, CR, Hingley-Wilson, S, Hackforth, S, Innes, J, Kon, OM, Lammas, DA, Minnikin, DE, Besra, GS et al, Willcox, BE and Lalvani, A (2011) A mycolic acid-specific CD1-restricted T cell population contributes to acute and memory immune responses in human tuberculosis infection. J Clin Invest, 121 (6). pp. 2493-2503.

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Abstract

Current tuberculosis (TB) vaccine strategies are largely aimed at activating conventional T cell responses to mycobacterial protein antigens. However, the lipid-rich cell wall of Mycobacterium tuberculosis (M. tuberculosis) is essential for pathogenicity and provides targets for unconventional T cell recognition. Group 1 CD1-restricted T cells recognize mycobacterial lipids, but their function in human TB is unclear and their ability to establish memory is unknown. Here, we characterized T cells specific for mycolic acid (MA), the predominant mycobacterial cell wall lipid and key virulence factor, in patients with active TB infection. MA-specific T cells were predominant in TB patients at diagnosis, but were absent in uninfected bacillus Calmette-Guérin-vaccinated (BCG-vaccinated) controls. These T cells were CD1b restricted, detectable in blood and disease sites, produced both IFN-γ and IL-2, and exhibited effector and central memory phenotypes. MA-specific responses contracted markedly with declining pathogen burden and, in patients followed longitudinally, exhibited recall expansion upon antigen reencounter in vitro long after successful treatment, indicative of lipid-specific immunological memory. T cell recognition of MA is therefore a significant component of the acute adaptive and memory immune response in TB, suggesting that mycobacterial lipids may be promising targets for improved TB vaccines.

Item Type:	Article
Authors :	Name Email ORCID Montamat-Sicotte, DJ Millington, KA Willcox, CR Hingley-Wilson, S s.hingley-wilson@surrey.ac.uk Hackforth, S Innes, J Kon, OM Lammas, DA Minnikin, DE Besra, GS Willcox, BE Lalvani, A
Date :	June 2011
Identification Number :	10.1172/JCI46216
Uncontrolled Keywords :	Acute Disease, Adaptive Immunity, Adult, Aged, Antigens, Bacterial, Antigens, CD1, Antitubercular Agents, BCG Vaccine, Cell Wall, Cells, Cultured, Female, Humans, Immunologic Memory, Interferon-gamma, Interleukin-2, Male, Middle Aged, Mycobacterium tuberculosis, Mycolic Acids, T-Cell Antigen Receptor Specificity, T-Lymphocyte Subsets, Tuberculosis, Tuberculosis Vaccines, Virulence, Young Adult
Depositing User :	Symplectic Elements
Date Deposited :	17 May 2017 09:42
Last Modified :	17 May 2017 14:44
URI:	http://epubs.surrey.ac.uk/id/eprint/824777

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