Journal Article

Immunosuppression during Active Tuberculosis Is Characterized by Decreased Interferon-γ Production and CD25 Expression with Elevated Forkhead Box P3, Transforming Growth Factor-β, and Interleukin-4 mRNA Levels

Beyers, Nulda, Walzl, Gerhard, Roberts, Teri, Aguirre, Ana

2007

Overview

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-Guérin (BCG)—stimulated peripheral blood mononuclear cells and whole blood cultures frompersons 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+CD25lo and CD4+CD25hi T cells, respectively. In case patients with active disease, BCG stimulation induced the lowest increase of CD25, CD4+CD25hi, CTLA-4, and interferon-γ. However, these case patients expressed the highest mRNA levels of forkhead box P3, transforming growth factor (TGF)-β, and interleukin (IL)-4 and a lower T-bet:GATA-3 ratio. There were no significant differences in IL-4δ2, IL-10, or TGF-β 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.

• Publisher: The University of Chicago Press,University of Chicago Press
• Subject: Antigen presenting cells / Antigens, CD - blood / Antigens, CD - genetics / Bacteria / Bacterial diseases / BCG Vaccine / Biological and medical sciences / Blood / CD3 Complex - genetics / CD4 Lymphocyte Count / Cytokines / DNA Primers / Forkhead Transcription Factors - genetics / Fundamental and applied biological sciences. Psychology / Gene Expression Regulation / Human bacterial diseases / Humans / Immunosuppression / Infections / Infectious diseases / Interferon-gamma - genetics / Interleukin-2 Receptor alpha Subunit - genetics / Interleukin-4 - genetics / Lymphocyte Count / Medical sciences / Messenger RNA / Microbiology / Mycobacterium tuberculosis / Polymerase Chain Reaction / Pulmonary tuberculosis / RNA, Messenger - genetics / T lymphocytes / T-Lymphocytes - immunology / Transforming Growth Factor beta - genetics / Tuberculosis / Tuberculosis - immunology / Tuberculosis and atypical mycobacterial infections