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 , 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.
Full text not available from this repository.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 | |||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Divisions : | Surrey research (other units) | |||||||||||||||||||||||||||||||||||||||
Authors : |
|
|||||||||||||||||||||||||||||||||||||||
Date : | June 2011 | |||||||||||||||||||||||||||||||||||||||
DOI : | 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 : | 24 Jan 2020 17:28 | |||||||||||||||||||||||||||||||||||||||
URI: | http://epubs.surrey.ac.uk/id/eprint/824777 |
Actions (login required)
![]() |
View Item |
Downloads
Downloads per month over past year