Activating and inhibitory Fcγ receptors can differentially module T cell-mediated autoimmunity

Mirentxu I. Iruretagoyena, Claudia A. Riedel, Eduardo D. Leiva, Miguel A. Gutiérrez, Sergio H. Jacbobelli, Alexis M. Kalergis

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

The molecular bases responsible for the loss of T cell tolerance tomyelin antigens leading to the onset of multiple sclerosis remain obscure. It has been shown that balanced signaling through activating and inhibitory receptors is critical for the maintenance of tolerance to self antigens in autoimmune disorders. However, although FcγR have been shown to influence experimental autoimmune encephalomyelitis (EAE) development, their role during pathogenesis remains controversial. Here we have evaluated whether relative expression of activating (FcγRIII) and inhibitory (FcγRIIb) FcγR can modulatemyelin-specific T cell response, as well as the susceptibility to develop EAE in mice. While FcγRIIb-/- mice showed a significant increase in EAE severity, an FcγRIII deficiency protected mice from disease. In addition, FcγRIIb-/- mice showed enhanced activation of myelin-specific effector T cells, which were significantly more effective at causing EAE in adoptive transfer experiments than were T cells from wild-type mice. In contrast, FcγRIII-/- mice showed a significantly reduced activation of myelin-specific T cells and these cells failed to adoptively transfer EAE. Consistently, increased expansion of regulatory T cells (Treg) during EAE was observed only for FcγRIII-/- mice, which were able to suppress disease when adoptively transferred to recipient mice. These findings suggest that the balance between activating and inhibitory FcγR signaling can contribute to the maintenance of T cell tolerance to myelin antigens and modulate EAE progression.

Original languageEnglish
Pages (from-to)2241-2250
Number of pages10
JournalEuropean Journal of Immunology
Volume38
Issue number8
DOIs
Publication statusPublished - Aug 2008

Keywords

  • Dendritic cells
  • EAE
  • FcγR
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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