help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
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
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200701-084OCv1
176/4/409    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hougardy, J.-M.
Right arrow Articles by Mascart, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hougardy, J.-M.
Right arrow Articles by Mascart, F.

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




This article has been cited by other articles:


Home page
 Eur Respir JHome page
K. Dheda, R. N. van Zyl-Smit, L. A. Sechi, M. Badri, R. Meldau, S. Meldau, G. Symons, P. L. Semple, A. Maredza, R. Dawson, et al.
Utility of quantitative T-cell responses versus unstimulated interferon-{gamma} for the diagnosis of pleural tuberculosis
Eur. Respir. J., November 1, 2009; 34(5): 1118 - 1126.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
L. Geffner, N. Yokobori, J. Basile, P. Schierloh, L. Balboa, M. M. Romero, V. Ritacco, M. Vescovo, P. Gonzalez Montaner, B. Lopez, et al.
Patients with Multidrug-Resistant Tuberculosis Display Impaired Th1 Responses and Enhanced Regulatory T-Cell Levels in Response to an Outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra Strains
Infect. Immun., November 1, 2009; 77(11): 5025 - 5034.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
K Dheda, R N van Zyl-Smit, R Meldau, S Meldau, G Symons, H Khalfey, N Govender, V Rosu, L A Sechi, A Maredza, et al.
Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis
Thorax, October 1, 2009; 64(10): 847 - 853.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
H. P. Windish, P. L. Lin, J. T. Mattila, A. M. Green, E. O. Onuoha, L. P. Kane, and J. L. Flynn
Aberrant TGF-{beta} signaling reduces T regulatory cells in ICAM-1-deficient mice, increasing the inflammatory response to Mycobacterium tuberculosis
J. Leukoc. Biol., September 1, 2009; 86(3): 713 - 725.
[Abstract] [Full Text] [PDF]

Home page
 CVIHome page
G. F. Black, B. A. Thiel, M. O. Ota, S. K. Parida, R. Adegbola, W. H. Boom, H. M. Dockrell, K. L. M. C. Franken, A. H. Friggen, P. C. Hill, et al.
Immunogenicity of Novel DosR Regulon-Encoded Candidate Antigens of Mycobacterium tuberculosis in Three High-Burden Populations in Africa
Clin. Vaccine Immunol., August 1, 2009; 16(8): 1203 - 1212.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. N. van Zyl-Smit, M. Pai, K. Peprah, R. Meldau, J. Kieck, J. Juritz, M. Badri, A. Zumla, L. A. Sechi, E. D. Bateman, et al.
Within-Subject Variability and Boosting of T-Cell Interferon-{gamma} Responses after Tuberculin Skin Testing
Am. J. Respir. Crit. Care Med., July 1, 2009; 180(1): 49 - 58.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Rahman, B. Gudetta, J. Fink, A. Granath, S. Ashenafi, A. Aseffa, M. Derbew, M. Svensson, J. Andersson, and S. G. Brighenti
Compartmentalization of Immune Responses in Human Tuberculosis: Few CD8+ Effector T Cells but Elevated Levels of FoxP3+ Regulatory T Cells in the Granulomatous Lesions
Am. J. Pathol., June 1, 2009; 174(6): 2211 - 2224.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
G. Meintjes, K. A. Wilkinson, M. X. Rangaka, K. Skolimowska, K. van Veen, M. Abrahams, R. Seldon, D. J. Pepper, K. Rebe, P. Mouton, et al.
Type 1 Helper T Cells and FoxP3-positive T Cells in HIV-Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome
Am. J. Respir. Crit. Care Med., November 15, 2008; 178(10): 1083 - 1089.
[Abstract] [Full Text] [PDF]

Home page
 CVIHome page
M. Feske, R. J. Nudelman, M. Medina, J. Lew, M. Singh, J. Couturier, E. A. Graviss, and D. E. Lewis
Enhancement of Human Antigen-Specific Memory T-Cell Responses by Interleukin-7 May Improve Accuracy in Diagnosing Tuberculosis
Clin. Vaccine Immunol., October 1, 2008; 15(10): 1616 - 1622.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
W. W. Yew and C. C. Leung
Update in Tuberculosis 2007
Am. J. Respir. Crit. Care Med., March 1, 2008; 177(5): 479 - 485.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2007 American Thoracic Society 		  Work-Life