Changes in the kinetics of intracellular IFN-gamma production in TB patients during treatment

The role of T lymphocyte cytokine responses in tuberculosis (TB) still needs clarification. This study aimed to define interferon-gamma (IFN-gamma) responses longitudinally in HIV-negative TB patients during treatment, compared to those of healthy volunteers. Flow cytometric intracellular IFN-gamma determinations after CD3 stimulation were done in parallel with lymphocyte proliferation assays in response to mycobacterial antigen. Percentages of IFN-gamma-producing CD8 and CD4 T lymphocytes in patients at diagnosis were significantly higher than in controls but normalized during treatment. Additional kinetic studies suggested accelerated IFN-gamma production in patients at diagnosis, compared to controls and treated patients. Lymphocyte proliferation was below normal in patients at diagnosis and increased rapidly with decreasing bacterial load during treatment. We conclude that T cell IFN-gamma response kinetics in TB patients suggest a pre-activated state at diagnosis, which changes during treatment. At diagnosis intracellular IFN-gamma or lymphocyte proliferation was not an indicator for treatment response.