Early dynamics of T helper cell cytokines and T regulatory cells in response to treatment of active Mycobacterium tuberculosis infection. (16th February 2015)

• Record Type: Journal Article
• Authors: Feruglio, S L; Tonby, K; Kvale, D; Dyrhol-Riise, A M
• Is Part Of: Clinical and experimental immunology. Volume 179:Number 3(2015:Mar.)
• Page Start: 454
• Page End: 465
• Publication Date: 2015-02-16
• Subjects: cytokines -- T cells -- treatment -- Tregs -- tuberculosis; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12468
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: 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)-γ, interleukin (IL)-2, tumour necrosis factor (TNF)-α] and degranulation (CD107a) as well as subsets of CD4 + T regulatory cells (Tregs ) 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-γ and single IFN-γ-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 Treg 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 + Tregs remained unchanged. The fraction of CD25 high CD127 low Tregs increased after 8 weeks of treatment. Thus, we revealed an opposing shift of Tregs 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.