Immunosuppression during active tuberculosis is characterized by decreased interferon- gamma production and CD25 expression with elevated forkhead box P3, transforming growth factor- beta , and interleukin-4 mRNA levels.
The balance between effector and regulatory responses after Mycobacterium tuberculosis infection may dictate outcome and progression to active disease. We investigated effector and regulatory T cell responses in bacille Calmette-Guerin (BCG)-stimulated peripheral blood mononuclear cells and whole blood cultures from persons with active tuberculosis (TB), persons with TB at the end of 6 months of treatment, and healthy control subjects with latent TB infection. All 3 groups displayed BCG-induced increases in effector and regulatory T cell phenotypes as defined by CD4(+)CD25(lo) and CD4(+)CD25(hi) T cells, respectively. In case patients with active disease, BCG stimulation induced the lowest increase of CD25, CD4(+)CD25(hi), CTLA-4, and interferon- gamma . However, these case patients expressed the highest mRNA levels of forkhead box P3, transforming growth factor (TGF)- beta , and interleukin (IL)-4 and a lower T-bet : GATA-3 ratio. There were no significant differences in IL-4 delta 2, IL-10, or TGF- beta receptor-II mRNA expression between groups. Together, these results suggest that immunosuppression seen after mycobacterial stimulation in case patients with active TB is associated with naturally occurring regulatory T cells.
Roberts
Teri
T
Molecular Biology and Human Genetics, Department of Biomedical Sciences, University of Stellenbosch, Cape Town, 7505, South Africa. teri@sun.ac.za
Beyers
Nulda
N
Aguirre
Ana
A
Walzl
Gerhard
G
D015703:Antigens, CD / Q000097:blood / Q000235:genetics; D001500:BCG Vaccine; D017252:CD3 Complex / Q000235:genetics; D018791:CD4 Lymphocyte Count; D017931:DNA Primers; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000235:genetics*; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D018655:Lymphocyte Count; D009169:Mycobacterium tuberculosis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics; D014376:Tuberculosis / Q000276:immunology*
D015703:Antigens, CD; D001500:BCG Vaccine; D017252:CD3 Complex; D017931:DNA Primers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma