1. A mycolic acid-specific CD1-restricted T cell population contributes to acute and memory immune responses in human tuberculosis infection.
- Author
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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
- Subjects
- Acute Disease, Adaptive Immunity, Adult, Aged, Antitubercular Agents therapeutic use, BCG Vaccine immunology, Cells, Cultured immunology, Female, Humans, Interferon-gamma metabolism, Interleukin-2 metabolism, Male, Middle Aged, Mycobacterium tuberculosis pathogenicity, T-Lymphocyte Subsets metabolism, Tuberculosis drug therapy, Tuberculosis prevention & control, Tuberculosis Vaccines, Virulence, Young Adult, Antigens, Bacterial immunology, Antigens, CD1 immunology, Cell Wall immunology, Immunologic Memory immunology, Mycobacterium tuberculosis immunology, Mycolic Acids immunology, T-Cell Antigen Receptor Specificity, T-Lymphocyte Subsets immunology, Tuberculosis immunology
- 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.
- Published
- 2011
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