title: Reduction of peripheral blood T cells producing IFN-γ and IL-17 after therapy with abatacept for rheumatoid arthritis.
abstract: OBJECTIVE
  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.
authors.affiliation: Rheumatology and Clinical Immunology Unit, Spedali Civili and University of Brescia, Italy. mirko_scarsi@libero.it.
authors.forename: M
authors.initials: M
authors.lastname: Scarsi
authors.forename: C
authors.initials: C
authors.lastname: Zanotti
authors.forename: M
authors.initials: M
authors.lastname: Chiarini
authors.forename: L
authors.initials: L
authors.lastname: Imberti
authors.forename: S
authors.initials: S
authors.lastname: Piantoni
authors.forename: M
authors.initials: M
authors.lastname: Frassi
authors.forename: A
authors.initials: A
authors.lastname: Tincani
authors.forename: P
authors.initials: P
authors.lastname: Airò
mesh_terms: D000069594:Abatacept; D000328:Adult; D018501:Antirheumatic Agents / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D007371:Interferon-gamma / Q000032:analysis / Q000097:blood; D059425:Interferon-gamma Release Tests; D020381:Interleukin-17 / Q000032:analysis / Q000097:blood; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D018796:Immunoconjugates; D020381:Interleukin-17; D000069594:Abatacept; D007371:Interferon-gamma