Reduction of peripheral blood T cells producing IFN-γ and IL-17 after therapy with abatacept for rheumatoid arthritis

Clin Exp Rheumatol. Mar-Apr 2014;32(2):204-10. Epub 2014 Jan 14.

Abstract

Objectives: Abatacept (ABA), a molecule used in the treatment of rheumatoid arthritis (RA), competes with the engagement of CD28, a T-cell receptor for co-stimulatory signals. CD28-mediated signalling regulates several T-cell functions, including inflammatory cytokine production and regulatory T cells (Treg) differentiation. Therefore, our objective was to evaluate the effects of ABA on peripheral blood T-lymphocyte cytokine production and on the number of circulating Treg.

Methods: In 24 RA patients treated with ABA for at least 6 months the proportions and absolute numbers of peripheral blood T cells producing interferon-gamma (IFN-γ) and interleukin-17 (IL-17) after in vitro stimulation, as well as those of Treg were longitudinally evaluated by flow cytometry.

Results: At baseline, compared with 16 healthy controls, RA patients had a higher percentage of CD4+ and CD8+ T cells producing IL-17 (p=0.021, and p=0.006, respectively), as well as of circulating Treg (p=0.041). After 6 months of therapy with ABA, there was a decrease of the percentage of IFN-γ- and IL-17-producing CD8+ T cells (p=0.033 and p=0.035, respectively), and of Treg (p=0.008), while that of IL-17-producing CD4+ T cells decreased after 12 months of treatment (p=0.005). The number of IL-17-producing T cells and of Treg, higher than in controls at baseline, normalised after ABA therapy. All these variations were statistically significant only in RA patients with EULAR good clinical response (n=17).

Conclusions: The blockade of CD28 signal caused by ABA induces the decrease in peripheral blood of IL-17- and IFN-γ-producing T cells.

Publication types

  • Clinical Trial

MeSH terms

  • Abatacept
  • Adult
  • Antirheumatic Agents / pharmacology
  • Arthritis, Rheumatoid* / blood
  • Arthritis, Rheumatoid* / drug therapy
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Humans
  • Immunoconjugates / pharmacology*
  • Interferon-gamma Release Tests
  • Interferon-gamma* / analysis
  • Interferon-gamma* / blood
  • Interleukin-17* / analysis
  • Interleukin-17* / blood
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Immunoconjugates
  • Interleukin-17
  • Abatacept
  • Interferon-gamma