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Published ahead of print on May 31, 2007, doi:10.1164/rccm.200701-084OC
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American Journal of Respiratory and Critical Care Medicine Vol 176. pp. 409-416, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200701-084OC

Original Article

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

Jean-Michel Hougardy1, Sammy Place1, Marc Hildebrand2, Annie Drowart3, Anne-Sophie Debrie4,5, Camille Locht4,5 and Françoise Mascart1,6

1 Laboratory of Vaccinology and Mucosal Immunity, Hôpital Erasme, Brussels, Belgium; 2 Infectious Disease Department, Hôpital Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium; 3 Chest Department, Hôpital Brugmann, Université Libre de Bruxelles, Brussels, Belgium; 4 Institut Pasteur de Lille, Lille, France; 5 INSERM, U629, Lille, France; and 6 Immunobiology Clinic, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium

Correspondence and requests for reprints should be addressed to Professor Françoise Mascart, Hôpital Erasme, Immunobiology Clinic, 808 Route de Lennik, B-1070 Brussels, Belgium. 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. 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+CD25highFOXP3+ 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+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 • heparin-binding hemagglutinin


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Elevated levels of regulatory T cells with the CD4+CD25+FOXP3+ phenotype have been detected in patients with tuberculosis.

What This Study Adds to the Field
We show that regulatory T cells suppress IFN-{gamma} responses preferably to protective antigens, such as the novel heparin-binding hemagglutinin, suggesting that the induction of these cells constitutes an important escape mechanism of Mycobacterium tuberculosis.

 



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