Early dynamics of T helper cell cytokines and T regulatory cells in response to treatment of active Mycobacterium tuberculosis infection. (March 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: 2015-03
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12468
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>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<sup>+</sup> T regulatory cells (T<sub>regs</sub>) after <italic>in‐vitro Mycobacterium tuberculosis</italic> (<italic>Mtb</italic>) 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 <italic>Mtb</italic>‐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<sup>+</sup> cells increased over time for both CD4<sup>+</sup> and CD8<sup>+</sup> T cells. The T<sub>reg</sub> subsets CD25<sup>high</sup>CD127<sup>low</sup>, CD25<sup>high</sup>CD147<sup>++</sup> and CD25<sup>high</sup>CD127<sup>low</sup>CD161<sup>+</sup> expanded significantly after <italic>Mtb</italic> antigen stimulation <italic>in vitro</italic> at all time‐points, whereas the CD25<sup>high</sup>CD127<sup>low</sup>CD39<sup>+</sup> T<sub>regs</sub> remained unchanged. The fraction of CD25<sup>high</sup>CD127<sup>low</sup> T<sub>regs</sub> increased after 8 weeks of treatment. Thus, we revealed an opposing shift of T<sub>regs</sub> and intracellular cytokine production during treatment. This may indicate that functional signatures of the CD4<sup>+</sup> and CD8<sup>+</sup> 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.</p> </abstract>