T regulatory cells and immune activation in Mycobacterium tuberculosis infection and the effect of preventive therapy

Mycobacterium tuberculosis (TB) often causes persistent infection and many immune cell subsets and regulatory mechanisms may operate throughout the various stages of infection. We have studied dendritic cell (DC) subsets, regulatory T cells (Treg) and the expression of activation and apoptosis markers on CD4+ and CD8+ T cells in blood from patients with active TB (n=20), subjects with positive QuantiFERON-TB GOLD (QFT) test (LTBI, latent TB infection) (n=20) before and after 3 months of preventive anti-tuberculous therapy and from QFT-negative controls (n=28). The frequency of CD4+ CD25+ CD127⁻ Treg was highest in the group with active TB (P=0.001), but also increased in the LTBI group (P=0.006) compared to controls. The highest level of activated T cells, defined as CD38+ HLA-DR+ cells, was found in the active TB group, for the CD4+ T cell subset positively correlated to the level of CD25+ CD127⁻ Treg (P<0.001, r=0.4268). After 3 months of preventive therapy, there was an increase in the fraction of foxp3+ Treg, but no differences in markers of activation or apoptosis. In conclusion, there seems to be an increased level of immune activation and Treg in both latent and active TB infection that is only modestly influenced by preventive therapy.