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

Clin Exp Immunol. 2015 Mar;179(3):454-65. doi: 10.1111/cei.12468.

Abstract

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.

Keywords: T cells; Tregs; cytokines; treatment; tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases
  • Adult
  • Aged
  • Antigens, Bacterial / metabolism
  • Antigens, CD / metabolism
  • Antitubercular Agents / therapeutic use*
  • Bacterial Proteins / metabolism
  • Biomarkers, Pharmacological / metabolism
  • Cells, Cultured
  • Cytokines / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Immunophenotyping
  • Male
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Mycobacterium tuberculosis / immunology*
  • Peptide Fragments / metabolism
  • Prospective Studies
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Treatment Outcome
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / immunology
  • Young Adult

Substances

  • Antigens, Bacterial
  • Antigens, CD
  • Antitubercular Agents
  • Bacterial Proteins
  • Biomarkers, Pharmacological
  • CFP-10 protein (71-85), Mycobacterium tuberculosis
  • Cytokines
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Peptide Fragments
  • Acyltransferases
  • antigen 85A, Mycobacterium tuberculosis