Enrichment of regulatory T-cells in blood of patients with multidrug-resistant tuberculosis.

ABSTRACT

OBJECTIVE: To measure the percentage of regulatory T-cells (Treg) and the expression of signalling molecules in these cells from the peripheral blood of patients with multidrug-resistant tuberculosis (MDR-TB). DESIGN: Patients with drug-susceptible tuberculosis (S-TB), MDR-TB and healthy controls (HCs) were recruited into the study. Levels of CD4(+)CD25(+)Foxp3(+) Treg cells from peripheral blood, and programmed death-1 (PD-1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and inducible costimulatory (ICOS) molecule expression in the cells were measured using flow cytometry. Suppression mediated by Treg cells was assessed in carboxyfluorescein succinimidyl ester (CFSE) based suppression assays with autologous CD4(+)CD25(-) T-effector (Teff) cells. RESULTS: Presence of Mycobacterium tuberculosis resulted in a higher proportion of Treg cells in S-TB patients than in HCs, and even higher levels in MDR-TB patients. Moreover, Treg cells in MDR-TB patients constitutively expressed high-level PD-1, CTLA-4 and ICOS. In addition, when cultured with activated CD4(+)CD25(-) Teff cells, Treg cells potently suppressed proliferation of Teff cells. CONCLUSIONS: The high level of Treg cells found in the peripheral blood of tuberculosis patients may partly explain the poor immune response against M. tuberculosis, and could be a marker of MDR-TB.