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

Abstract

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 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+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. © 2007 by the Infectious Diseases Society of America. All rights reserved.