IL-17-producing CD4(+) T cells contribute to the loss of B-cell tolerance in experimental autoimmune myasthenia gravis

Hanne Schaffert, Andreas Pelz, Abhishek Saxena, Mario Losen, Andreas Meisel, Andreas Thiel, Siegfried Kohler*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Web of Science)

Abstract

The role of Th17 cells in the pathogenesis of autoantibody-mediated diseases is unclear. Here, we assessed the contribution of Th17 cells to the pathogenesis of experimental autoimmune myasthenia gravis (EAMG), which is induced by repetitive immunizations with Torpedo californica acetylcholine receptor (tAChR). We show that a significant fraction of tAChR-specific CD4(+) T cells is producing IL-17. IL-17(ko) mice developed fewer or no EAMG symptoms, although the frequencies of tAChR-specific CD4(+) T cells secreting IL-2, IFN-, or IL-21, and the percentage of FoxP3(+) T-reg cells were similar to WT mice. Even though the total anti-tAChR antibody levels were equal, the complement fixating IgG2b subtype was reduced in IL-17(ko) as compared to WT mice. Most importantly, pathogenic anti-murine AChR antibodies were significantly lower in IL-17(ko) mice. Furthermore, we confirmed the role of Th17 cells in EAMG pathogenesis by the reconstitution of TCR /(ko) mice with WT or IL-17(ko) CD4(+) T cells. In conclusion, we show that the level of IgG2b and the loss of B-cell tolerance, which results in pathogenic anti-murine AChR-specific antibodies, are dependent on IL-17 production by CD4(+) T cells. Thus, we describe here for the first time how Th17 cells are involved in the induction of classical antibody-mediated autoimmunity.
Original languageEnglish
Pages (from-to)1339-1347
JournalEuropean Journal of Immunology
Volume45
Issue number5
DOIs
Publication statusPublished - May 2015

Keywords

  • Autoantibodies
  • B-cell tolerance
  • Experimental autoimmune myasthenia gravis
  • IL-17
  • IgG subtypes
  • Th17 cells

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