Role of gamma/delta T-cells in the peripheral blood of patients with pulmonary tuberculosis

Abstract

Although gamma/delta T-cells are known to contain the highest frequency of mycobacteria-reactive cells in humans, and recent studies have suggested that they play an important role in the initial immune response to Mycobacterium tuberculosis (Mtb), very few studies have attempted to analyze these cells in patients with active pulmonary tuberculosis (TB). The aim of the present study was therefore to evaluate the gamma/delta T-cell populations present in the peripheral blood and the IFN-gamma production of gamma/delta T-cells stimulated by PMA before and after anti-TB chemotherapy in patients in the initial treatment stage for primary active pulmonary TB. Cell populations were measured by three-color flow cytometry of peripheral blood mononuclear cells. We compared the population of gamma/delta T-cells and the production of IFN-gamma between normal healthy controls and TB patients. Absolute numbers of gamma/delta T-cells remained constant in the peripheral blood of TB patients. However, production of IFN-gamma in gamma/delta T-cells was dramatically suppressed prior to anti-TB chemotherapy in comparison with healthy control subjects, and further reduced following anti-TB chemotherapy. We also examined the influence of isoniazid (INH) in anti-TB chemotherapy. INH suppressed IFN-gamma production of gamma/delta and alpha/beta T-cells. The findings demonstrated a strong correlation between the production of IFN-gamma in gamma/delta T-cells and manifestation of primary active pulmonary TB, which was consistent with the hypothesized role for gamma/delta T-cells in the protective immune response to Mtb infection.