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

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.