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Published ahead of print on May 31, 2007, doi:10.1164/rccm.200701-084OC

Am. J. Respir. Crit. Care Med., Volume 176, Number 4, August 2007, 409-416

A more recent version of this article appeared on August 15, 2007
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Submitted on January 16, 2007
Accepted on May 31, 2007

Regulatory T Cells Depress Immune Responses to Protective Antigens in Active Tuberculosis

Jean-Michel Hougardy1, Sammy Place1, Marc Hildebrand2, Annie Drowart3, Anne-Sophie Debrie4, Camille Locht4, and Francoise Mascart1*

1 Laboratory of Vaccinology and Mucosal Immunity, Hopital Erasme, Universite Libre de Bruxelles (U.L.B.), Brussels, Belgium, 2 Infectious Disease Department, Hopital Saint-Pierre, Universite Libre de Bruxelles (U.L.B.), Brussels, Belgium, 3 Chest Department, Hopital Brugmann, Universite Libre de Bruxelles (U.L.B.), Brussels, Belgium, 4 Institut Pasteur de Lille, Lille, France; INSERM U629, Lille, France

* To whom correspondence should be addressed. E-mail: fmascart{at}ulb.ac.be.

Rationale: Tuberculosis (TB) remains a leading cause of death, and the role of T cell responses to control Mycobacterium tuberculosis infections is well recognized. Subjects with latent TB infection (LTBI) 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-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: Whereas 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+CD25highFOXP3+ T lymphocytes resulted in the induction by HBHA of IFN-{gamma} concentrations that reached levels similar to those obtained for LTBI. No effect was noted on the ESAT-6 or candidin T cell responses. Conclusion: Specific CD4+CD25highFOXP3+ T cells depress the T cell mediated immune responses to the protective mycobacterial antigen HBHA during active TB in humans.


Key words: Tuberculosis, Regulatory T cells, HBHA




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