EAE mediated by a non-IFN-γ/non-IL-17 pathway

Eur J Immunol. 2010 Aug;40(8):2340-8. doi: 10.1002/eji.201040489.


Previous studies have shown that EAE can be elicited by the adoptive transfer of either IFN-γ-producing (Th1) or IL-17-producing (Th17) myelin-specific CD4(+) T-cell lines. Paradoxically, mice deficient in either IFN-γ or IL-17 remain susceptible to EAE following immunization with myelin antigens in CFA. These observations raise questions about the redundancy of IFN-γ and IL-17 in autoimmune demyelinating disease mediated by a diverse, polyclonal population of autoreactive T cells. In this study, we show that an atypical form of EAE, induced in C57BL/6 mice by the adoptive transfer of IFN-γ-deficient effector T cells, required IL-17 signaling for the development of brainstem infiltrates. In contrast, classical EAE, characterized by predominant spinal cord inflammation, occurred in the combined absence of IFN-γ and IL-17 signaling, but was dependent on GM-CSF and CXCR2. Our findings contribute to a growing body of data, indicating that individual cytokines vary in their importance across different models of CNS autoimmunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Brain Stem / immunology*
  • Brain Stem / pathology
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Immunization
  • Interferon-gamma / genetics*
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / immunology
  • Myelin-Associated Glycoprotein / metabolism
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Receptors, Interleukin-8B / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Spinal Cord / immunology
  • Spinal Cord / pathology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology
  • T-Lymphocytes / transplantation


  • Interleukin-17
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Receptors, Interleukin-8B
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor