Beta interferon restricts the inflammatory potential of CD4+ cells through the boost of the Th2 phenotype, the inhibition of Th17 response and the prevalence of naturally occurring T regulatory cells

Beta-interferon (IFN-β) is a valuable therapy for multiple sclerosis (MS) which is also effective in the animal model of experimental autoimmune encephalomyelitis (EAE). However, the accurate mechanisms to explain its anti-inflammatory activity in the disease are not fully revealed. Available data support that T lymphocytes are among the main cell targets of IFN-β. We have found that in vitro anti-CD3 stimulation of uncommitted murine naïve T cells under IFN-β treatment results in skewing the T cell differentiation process towards the T2 phenotype, in a prevention from apoptosis of naturally occurring CD4+ T regulatory cells (nTreg) in correlation with an increase in Bcl-xL expression, and in a decrease of IL-17 expression. Elimination of nTreg from the primary culture of naïve CD4+ cells abolished the down-regulation of IL-17 driven by IFN-β, what suggests the interaction between Th17 and nTreg subsets. Experiments in EAE induced in SJL mice, showed in vivo evidence for the accumulation of spleen CD4+CD25+GITR+Foxp3+ cells after IFN-β treatment. On the other hand, treated animals showed a striking decrease of IL-17 expression by peripheral CD4+ cells (Th17) and MBP-specific spinal cord cells. Both the in vivo and in vitro results point out new targets through which IFN-β could exert its therapeutic action.