Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
A mycolic acid–specific CD1-restricted T cell population contributes to acute and memory immune responses in human tuberculosis infection
Damien J. Montamat-Sicotte, … , Benjamin E. Willcox, Ajit Lalvani
Damien J. Montamat-Sicotte, … , Benjamin E. Willcox, Ajit Lalvani
Published May 16, 2011
Citation Information: J Clin Invest. 2011;121(6):2493-2503. https://doi.org/10.1172/JCI46216.
View: Text | PDF
Research Article Immunology Article has an altmetric score of 14

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

  • Text
  • PDF
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

×

Figure 7

Expansion of MA-specific T cell responses from the blood of TB patients more than 6 months after curative treatment.

Options: View larger image (or click on image) Download as PowerPoint
Expansion of MA-specific T cell responses from the blood of TB patients ...
PBLs from (A) 2 healthy donors (H13, H14) and (B) 3 TB patients (A15, A16, and A55 bled 27, 21, and 11 months after initiation of treatment, respectively, and 10 months later) were incubated for 14 days in the presence of blood monocyte–derived DCs pulsed with PI, MA, ESAT-6, or PPD. Cultured T cells were then harvested and restimulated with blood-derived DCs pulsed with their respective antigens, and results analyzed by ELISpot. (C) Direct ex vivo staining of uncultured PBLs from patients A55 and A16 (21 and 37 months after treatment initiation, respectively). PBLs were incubated in the presence of monocyte-derived DCs pulsed with PI, MA, or ESAT-6. IFN-γ– and IL-2–producing T cells were enriched through magnetic separation and stained with anti-CD3, anti-CD4, anti-CD8, anti-CCR7, and anti-CD45RA. Stained cells were analyzed by flow cytometry. Circles represent positive dual IFN-γ/IL-2–secreting T cells (top right quadrants); positive IL-2–only–secreting T cells (top left quadrants); and positive IFN-γ–only–secreting T cells (bottom right quadrants). Percentages of live CD3+ cells are shown in each quadrant in which a response was present.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Blogged by 1
Referenced in 4 patents
135 readers on Mendeley
1 readers on CiteULike
See more details