Teriflunomide prevents the activation-induced CD25 expression on canine CD4+ T cells

Abstract Teriflunomide (TER) is an immunomodulatory agent. First reports on the use of TER in dogs have already appeared. Immune mechanisms underlying the immunosuppressive and anti-inflammatory properties of TER are not completely understood. The study attempts to shed light on the involvement of CD4+ T cells in inducing these properties in dogs. This study investigates the effect of TER on CD25 and Foxp3 expression by canine CD4+T cells in the course of in vitro activation. CD25 is T cell activation marker, whereas Foxp3 is critical for the development and function of CD4+ regulatory T (Treg) cells. Peripheral blood mononuclear cells collected from clinically healthy dogs (n = 15) were exposed to TER at concentrations reflecting its plasma levels obtained at a typical dose and at a ten-fold lower concentration with PMA/ionomycin stimulation. The percentage of CD25-expressing cells within CD4+ T cell subset in the culture treated with TER 10−4 M did not differ significantly from the value of this parameter in untreated non-stimulated cells but was significantly lower than that in untreated stimulated cells. The exposure to TER 10−4 M led to a significant increase in the percentage of Foxp3-expressing cells within the CD4+ T cell subset. However, the exposure to the lower concentration of TER did not affect the evaluated parameters. The results indicate that TER at the concentration achieved at a therapeutic dose prevented the activation-induced CD25 expression and induced Foxp3 expression by canine CD4+ T cells. These results suggest that the generation of inducible Foxp3-expressing CD4+ T cells and inhibition of CD4+ T cell activation may constitute one of the mechanisms responsible for the immunosuppressive and anti-inflammatory properties of TER.