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-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.

• Authors: Damien J Montamat-Sicotte, Kerry A Millington, Carrie R Willcox, Suzie Hingley-Wilson, Sarah Hackforth, John Innes, Onn Min Kon, David A Lammas, David E Minnikin, Gurdyal S Besra, Benjamin E Willcox, Ajit Lalvani
• Journal: The Journal of clinical investigation (J Clin Invest) Vol. 121 Issue 6 Pg. 2493-503 (Jun 2011) ISSN: 1558-8238 [Electronic] United States
• PMID: 21576820 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Antigens, CD1
• Antitubercular Agents
• BCG Vaccine
• Interleukin-2
• Mycolic Acids
• Tuberculosis Vaccines
• Interferon-gamma

Topics

• Acute Disease
• Adaptive Immunity
• Adult
• Aged
• Antigens, Bacterial (immunology)
• Antigens, CD1 (immunology)
• Antitubercular Agents (therapeutic use)
• BCG Vaccine (immunology)
• Cell Wall (immunology)
• Cells, Cultured (immunology)
• Female
• Humans
• Immunologic Memory (immunology)
• Interferon-gamma (metabolism)
• Interleukin-2 (metabolism)
• Male
• Middle Aged
• Mycobacterium tuberculosis (immunology, pathogenicity)
• Mycolic Acids (immunology)
• T-Cell Antigen Receptor Specificity
• T-Lymphocyte Subsets (immunology, metabolism)
• Tuberculosis (drug therapy, immunology, prevention & control)
• Tuberculosis Vaccines
• Virulence
• Young Adult