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

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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, Carrie; Hingley-Wilson, S; Hackforth, S; Innes, J; Kon, OM; Lammas, David; Minnikin, David; Besra, Gurdyal; Willcox, Benjamin; Lalvani, A.

In: Journal of Clinical Investigation, Vol. 121, No. 6, 01.06.2011, p. 2493-2503.

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@article{3509b10a20dd475d91aa192d8244fc17,
title = "A mycolic acid-specific CD1-restricted T cell population contributes to acute and memory immune responses in human tuberculosis infection",
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-Guerin-vaccinated (BCG-vaccinated) controls. These T cells were CD1b restricted, detectable in blood and disease sites, produced both IFN-gamma 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.",
author = "DJ Montamat-Sicotte and KA Millington and Carrie Willcox and S Hingley-Wilson and S Hackforth and J Innes and OM Kon and David Lammas and David Minnikin and Gurdyal Besra and Benjamin Willcox and A Lalvani",
year = "2011",
month = jun
day = "1",
doi = "10.1172/JCI46216",
language = "English",
volume = "121",
pages = "2493--2503",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "American Society for Clinical Investigation",
number = "6",

}

RIS

TY - JOUR

T1 - A mycolic acid-specific CD1-restricted T cell population contributes to acute and memory immune responses in human tuberculosis infection

AU - Montamat-Sicotte, DJ

AU - Millington, KA

AU - Willcox, Carrie

AU - Hingley-Wilson, S

AU - Hackforth, S

AU - Innes, J

AU - Kon, OM

AU - Lammas, David

AU - Minnikin, David

AU - Besra, Gurdyal

AU - Willcox, Benjamin

AU - Lalvani, A

PY - 2011/6/1

Y1 - 2011/6/1

N2 - 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-Guerin-vaccinated (BCG-vaccinated) controls. These T cells were CD1b restricted, detectable in blood and disease sites, produced both IFN-gamma 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.

AB - 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-Guerin-vaccinated (BCG-vaccinated) controls. These T cells were CD1b restricted, detectable in blood and disease sites, produced both IFN-gamma 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.

U2 - 10.1172/JCI46216

DO - 10.1172/JCI46216

M3 - Article

C2 - 21576820

VL - 121

SP - 2493

EP - 2503

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 6

ER -