Heparin-binding, hemagglutinin-specific IFN-gamma synthesis at the site of infection during active tuberculosis in humans.

Abstract

RATIONALE:

Tuberculosis (TB) remains a major cause of mortality. A better understanding of the immune responses to mycobacterial antigens may be helpful to develop improved vaccines and diagnostics.

OBJECTIVES:

The mycobacterial antigen heparin-binding hemagglutinin (HBHA) induces strong IFN-γ responses by circulating lymphocytes from subjects latently infected with Mycobacterium tuberculosis, and low responses associated with CD4(+) regulatory T (Treg) cells in patients with TB. Here, we investigated HBHA-specific IFN-γ responses at the site of the TB disease.

METHODS:

Bronchoalveolar lavages, pleural fluids, and blood were prospectively collected from 61 patients with a possible diagnosis of pulmonary or pleural TB. HBHA-specific IFN-γ production was analyzed by flow cytometry and ELISA. The suppressive effect of pleural Treg cells was investigated by depletion experiments.

MEASUREMENTS AND MAIN RESULTS:

The percentages of HBHA-induced IFN-γ(+) alveolar and pleural lymphocytes were higher for pulmonary (P < 0.0001) and for pleural (P < 0.01) TB than for non-TB controls. Local CD4(+) and CD8(+) T cells produced the HBHA-specific IFN-γ. This local secretion was not suppressed by Treg lymphocytes, contrasting with previously reported data on circulating lymphocytes.

CONCLUSIONS:

Patients with TB display differential effector and regulatory T-cell responses to HBHA in local and circulating lymphocytes with a predominant effector CD4(+) and CD8(+) response locally, compared with a predominant Treg response among circulating lymphocytes. These findings may be helpful for the design of new vaccines against TB, and the detection of HBHA-specific T cells at the site of the infection may be a promising tool for the rapid diagnosis of active TB.

• Authors: Sammy Place, Virginie Verscheure, Nour de San, Jean-Michel Hougardy, Kinda Schepers, Violette Dirix, Anne Dediste, Olivier Michel, Annie Drowart, Sabine D Allard, T Mark Doherty, Sophie Lecher, Camille Locht, Françoise Mascart
• Journal: American journal of respiratory and critical care medicine (Am J Respir Crit Care Med) Vol. 182 Issue 6 Pg. 848-54 (Sep 15 2010) ISSN: 1535-4970 [Electronic] United States
• PMID: 20508213 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Lectins
• heparin-binding hemagglutinin
• Interferon-gamma

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antigens, Bacterial (immunology)
• Bronchoalveolar Lavage Fluid (cytology, immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Humans
• Interferon-gamma (biosynthesis)
• Lectins (immunology)
• Male
• Middle Aged
• Mycobacterium tuberculosis (immunology)
• Prospective Studies
• T-Lymphocytes, Regulatory (immunology)
• Tuberculosis, Pleural (blood, immunology, microbiology)
• Tuberculosis, Pulmonary (blood, immunology, microbiology)
• Young Adult