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

Mol Immunol. 2008 Sep;45(15):4008-19. doi: 10.1016/j.molimm.2008.06.006. Epub 2008 Jul 18.


Beta-interferon (IFN-beta) 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-beta. We have found that in vitro anti-CD3 stimulation of uncommitted murine naïve T cells under IFN-beta 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-beta, 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-beta 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-beta could exert its therapeutic action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Interferon-beta / immunology
  • Interferon-beta / pharmacology*
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / immunology*
  • Mice
  • Mice, Inbred C3H
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology
  • Th2 Cells / cytology
  • Th2 Cells / immunology*


  • Interleukin-17
  • Interferon-beta