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-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.

Patients with Multidrug-Resistant Tuberculosis Display Impaired Th1 Responses and Enhanced Regulatory T-Cell Levels in Response to an Outbreak of Multidrug-ResistantMycobacterium tuberculosisM and Ra Strains

“…ϩ Treg cells are expanded in vivo in MDR-TB patients and confirm previous reports that detected CD4 ϩ Treg cell expansion in S-TB patients (6,18,19,46).…”

“…Nevertheless, an excessive Th1 downregulation might favor disease progression. In this context, increased levels of CD4 ϩ CD25 high Foxp3 ϩ Treg cells have been detected in PBMC from drug-susceptible tuberculosis (S-TB) patients compared to those from PPDpositive (PPD ϩ ) healthy donors (18)(19)(20)46). In addition, the results of studies involving in vitro depletion of CD4 ϩ…”

The use of Mycobacterium tuberculosis HspX and GlcB proteins to identify latent tuberculosis in rheumatoid arthritis patients

“…Some authors believe that Treg cells are involved in the suppression of Mtb-specific Th1 cells ( Chen et al 2007 , Roberts et al 2007 ). Human CD4 + Treg cells can be distinguished from recently activated T cells (CD25 + ) by their expression of the nuclear transcription factor FOXP3 ( Fontenot et al 2003 , Roberts et al 2007 , Ellner 2010 ). Treg cells have been shown to regulate effector T cells ( Ribeiro-Rodrigues et al 2006 , Chen et al 2007 ).…”

Multifunctional CD4+ T cells correlate with active Mycobacterium tuberculosis infection

“…1 T cells, and other reported the absence of modulation of this T-cell subset [36][37][38][39][40]. Moreover, a recent study found that depletion of CD4 Figure 4.…”