Regulatory T cells depress immune responses to protective antigens in active tuberculosis.

Abstract

RATIONALE:

Tuberculosis (TB) remains a leading cause of death, and the role of T-cell responses to control Mycobacterium tuberculosis infections is well recognized. Patients with latent TB infection develop strong IFN-gamma responses to the protective antigen heparin-binding hemagglutinin (HBHA), whereas patients with active TB do not.

OBJECTIVES:

We investigated the mechanism of this difference and evaluated the possible involvement of regulatory T (Treg) cells and/or cytokines in the low HBHA T-cell responses of patients with active TB.

METHODS:

The impact of anti-transforming growth factor (TGF)-beta and anti-IL-10 antibodies and of Treg cell depletion on the HBHA-induced IFN-gamma secretion was analyzed, and the Treg cell phenotype was characterized by flow cytometry.

MEASUREMENTS AND MAIN RESULTS:

Although the addition of anti-TGF-beta or anti-IL-10 antibodies had no effect on the HBHA-induced IFN-gamma secretion in patients with active TB, depletion of CD4(+)CD25(high)FOXP3(+) T lymphocytes resulted in the induction by HBHA of IFN-gamma concentrations that reached levels similar to those obtained for latent TB infection. No effect was noted on the early-secreted antigen target-6 or candidin T-cell responses.

CONCLUSIONS:

Specific CD4(+)CD25(high)FOXP3(+) T cells depress the T-cell-mediated immune responses to the protective mycobacterial antigen HBHA during active TB in humans.

• Authors: Jean-Michel Hougardy, Sammy Place, Marc Hildebrand, Annie Drowart, Anne-Sophie Debrie, Camille Locht, Francoise Mascart
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 176 Issue 4 Pg. 409-16 (Aug 15 2007) ISSN: 1073-449X [Print] United States
• PMID: 17541018 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• CD4 Antigens
• FOXP3 protein, human
• Forkhead Transcription Factors
• Interleukin-2 Receptor alpha Subunit
• Lectins
• heparin-binding hemagglutinin
• Interferon-gamma

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• CD4 Antigens (metabolism)
• Cell Proliferation
• Flow Cytometry
• Forkhead Transcription Factors (metabolism)
• Humans
• Interferon-gamma (biosynthesis)
• Interleukin-2 Receptor alpha Subunit (metabolism)
• Lectins (immunology)
• Lymphocyte Depletion
• Middle Aged
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Tuberculosis (immunology)