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Am J Respir Crit Care Med. 2007 Aug 15;176(4):409-16. Epub 2007 May 31.

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

Author information

1
Laboratory of Vaccinology and Mucosal Immunity, Hôpital Erasme, Brussels, Belgium.

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.

PMID:
17541018
DOI:
10.1164/rccm.200701-084OC
[Indexed for MEDLINE]

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