Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment

B Molins, M Mesquida, R W J Lee, V Llorenç, L Pelegrín, A Adán

Research output: Contribution to journalArticle (Academic Journal)

Abstract

The aim of this study was to quantify the proportion of regulatory T cells (Treg ) and cytokine expression by peripheral blood mononuclear cells (PBMCs) in patients with active non-infectious uveitis, and to evaluate the effect of in-vitro treatment with infliximab, dexamethasone and cyclosporin A on Treg levels and cytokine production in PBMCs from uveitis patients and healthy subjects. We included a group of 21 patients with active non-infectious uveitis and 18 age-matched healthy subjects. The proportion of forkhead box protein 3 (FoxP3)(+) Treg cells and intracellular tumour necrosis factor (TNF)-α expression in CD4(+) T cells was determined by flow cytometry. PBMCs were also either rested or activated with anti-CD3/anti-CD28 and cultured in the presence or absence of dexamethasone, cyclosporin A and infliximab. Supernatants of cultured PBMCs were collected and TNF-α, interleukin (IL)-10, IL-17 and interferon (IFN)-γ levels were measured by enzyme-linked immunosorbent assay (ELISA). No significant differences were observed in nTreg levels between uveitis patients and healthy subjects. However, PBMCs from uveitis patients produced significantly higher amounts of TNF-α and lower amounts of IL-10. Dexamethasone treatment in vitro significantly reduced FoxP3(+) Treg levels in PBMCs from both healthy subjects and uveitis patients, and all tested drugs significantly reduced TNF-α production in PBMCs. Dexamethasone and cyclosporin A significantly reduced IL-17 and IFN-γ production in PBMCs and dexamethasone up-regulated IL-10 production in activated PBMCs from healthy subjects. Our results suggest that PBMCs from patients with uveitis express more TNF-α and less IL-10 than healthy subjects, and this is independent of FoxP3(+) Treg levels. Treatment with infliximab, dexamethasone and cyclosporin A in vitro modulates cytokine production, but does not increase the proportion of FoxP3(+) Treg cells.

Original languageEnglish
Pages (from-to)529-38
Number of pages10
JournalClinical and Experimental Immunology
Volume179
Issue number3
DOIs
Publication statusPublished - Mar 2015

Keywords

  • Adult
  • Antibodies, Monoclonal/pharmacology
  • Cells, Cultured
  • Cyclosporine/pharmacology
  • Cytokines/metabolism
  • Dexamethasone/pharmacology
  • Disease Progression
  • Female
  • Forkhead Transcription Factors/metabolism
  • Humans
  • Infliximab
  • Lymphocyte Count
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory/drug effects
  • Uveitis/drug therapy
  • Young Adult

Fingerprint Dive into the research topics of 'Regulatory T cell levels and cytokine production in active non-infectious uveitis: in-vitro effects of pharmacological treatment'. Together they form a unique fingerprint.

  • Cite this