Regulatory T cells depress immune responses to protective antigens in active tuberculosis.
BACKGROUND
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.


OBJECTIVE
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.


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(+)CD25(high)FOXP3(+) 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(+)CD25(high)FOXP3(+) T cells depress the T-cell-mediated immune responses to the protective mycobacterial antigen HBHA during active TB in humans.
Hougardy
Jean-Michel
JM
Laboratory of Vaccinology and Mucosal Immunity, Hôpital Erasme, Brussels, Belgium.
Place
Sammy
S
Hildebrand
Marc
M
Drowart
Annie
A
Debrie
Anne-Sophie
AS
Locht
Camille
C
Mascart
Francoise
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015704:CD4 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037102:Lectins / Q000276:immunology; D008212:Lymphocyte Depletion; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology*
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D037102:Lectins; C104578:heparin-binding hemagglutinin; D007371:Interferon-gamma