Association of synovial tissue polyfunctional T-cells with DAPSA in psoriatic arthritis

Ann Rheum Dis. 2019 Mar;78(3):350-354. doi: 10.1136/annrheumdis-2018-214138. Epub 2019 Jan 9.


Objective: This study examines polyfunctional T-cells in psoriatic arthritis (PsA) synovial tissue and their associations with clinical disease and implications for therapy.

Methods: PsA synovial tissue was enzymatically/mechanically digested to generate synovial tissue single cell suspensions. Frequencies of polyfunctional CD4, CD8, T-helper 1 (Th1), Th17 and exTh17 cells, using CD161 as a marker of Th17 plasticity, were determined by flow cytometry in matched PsA synovial tissue and peripheral blood. Synovial T-cell polyfunctionality was assessed in relation to Disease Activity in PSoriatic Arthritis (DAPSA) and in synovial cell suspensions cultured with a current mode of treatment, phosphodiesterase 4 (PDE4) inhibitor.

Results: PsA synovial tissue infiltrating CD4+ T-cells expressed higher levels of interleukin (IL)-17A, interferon gamma (IFN-γ), GM-CSF and CD161, with parallel enrichment of Th1, Th17 and exTh17 T-helper subsets (all p<0.05). Interestingly, a significant proportion of synovial T-cell subsets were triple-positive for GM-CSF, tumour necrosis factor (-TNF), -IL-17 or IFN-γ compared with matched blood (all p<0.05). Importantly, frequencies of polyfunctional T-cells correlated with DAPSA: Th1-GM-CSF+/TNF+/IFN-γ+ (r=0.7, p<0.01), Th17-GM-CSF+/TNF+/IL-17+ (r=0.6, p<0.057) and exTh17-GM-CSF+/TNF+/IFN-γ+ (r=0.7, p=0.0096), with no associations observed for single cytokine-producing T-cells. Following ex vivo culture of PsA synovial tissue cell suspensions, polyfunctional GM-CSF+TNFα+IL-17A+ or/IFN-γ+-producing T-cells (p<0.05), but not single cytokine-producing T-cells, were inhibited with a PDE4 inhibitor.

Conclusion: These data demonstrate enrichment of polyfunctional T-cells in PsA synovial tissue which were strongly associated with DAPSA and ex vivo therapeutic response.

Keywords: polyfunctional t-cells; psoriatic arthritis; synovial tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Psoriatic / immunology*
  • Arthritis, Psoriatic / physiopathology*
  • CD4 Antigens / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8 Antigens / drug effects
  • Cell Culture Techniques
  • Flow Cytometry
  • Humans
  • Interferon-gamma / drug effects
  • Interleukin-17 / immunology
  • Phosphodiesterase 4 Inhibitors / pharmacology
  • Severity of Illness Index
  • Synovial Membrane / cytology*
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • Th1 Cells / drug effects
  • Th17 Cells / drug effects
  • Tumor Necrosis Factor-alpha / immunology


  • CD4 Antigens
  • CD8 Antigens
  • IL17A protein, human
  • Interleukin-17
  • Phosphodiesterase 4 Inhibitors
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma