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


OBJECTIVE
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.


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.
Place
Sammy
S
Laboratory of Vaccinology and Mucosal Immunity, Hôpital Brugmann, Université Libre de Bruxelles, Brussels, Belgium.
Verscheure
Virginie
V
de San
Nour
N
Hougardy
Jean-Michel
JM
Schepers
Kinda
K
Dirix
Violette
V
Dediste
Anne
A
Michel
Olivier
O
Drowart
Annie
A
Allard
Sabine D
SD
Doherty
T Mark
TM
Lecher
Sophie
S
Locht
Camille
C
Mascart
Françoise
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D037102:Lectins / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014396:Tuberculosis, Pleural / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D055815:Young Adult
D000942:Antigens, Bacterial; D037102:Lectins; C104578:heparin-binding hemagglutinin; D007371:Interferon-gamma