Early dynamics of T helper cell cytokines and T regulatory cells in response to treatment of active Mycobacterium tuberculosis infection

Biomarkers that can identify tuberculosis (TB) disease and serve as markers for efficient therapy are requested. We have studied T cell cytokine production [interferon (IFN)-, interleukin (IL)-2, tumour necrosis factor (TNF)-] and degranulation (CD107a) as well as subsets of CD4(+) T regulatory cells (T-regs) after in-vitro Mycobacterium tuberculosis (Mtb) antigen stimulation [early secretory antigenic target (ESAT)-6, culture filtrate protein (CFP)-10, antigen 85 (Ag85)] in 32 patients with active tuberculosis (TB) disease throughout 24 weeks of effective TB treatment. A significant decline in the fraction of Mtb-specific total IFN- and single IFN--producing T cells was already observed after 2 weeks of treatment, whereas the pool of single IL-2(+)cells increased over time for both CD4(+) and CD8(+) T cells. The T-reg subsets CD25(high)CD127(low), CD25(high)CD147(++) and CD25(high)CD127(low)CD161(+) expanded significantly after Mtb antigen stimulation in vitro at all time-points, whereas the CD25(high)CD127(low)CD39(+) T-regs remained unchanged. The fraction of CD25(high)CD127(low) T-regs increased after 8 weeks of treatment. Thus, we revealed an opposing shift of T-regs and intracellular cytokine production during treatment. This may indicate that functional signatures of the CD4(+) and CD8(+) T cells can serve as immunological correlates of early curative host responses. Whether such signatures can be used as biomarkers in monitoring and follow-up of TB treatment needs to be explored further.