Abstract
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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adoptive Transfer
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Animals
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Brain Stem / immunology*
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Brain Stem / pathology
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Cells, Cultured
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Encephalomyelitis, Autoimmune, Experimental / genetics
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Encephalomyelitis, Autoimmune, Experimental / physiopathology
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Immunization
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Interferon-gamma / genetics*
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Interleukin-17 / genetics
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Interleukin-17 / immunology
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Interleukin-17 / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Myelin Proteins
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Myelin-Associated Glycoprotein / immunology
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Myelin-Associated Glycoprotein / metabolism
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Receptors, Interleukin-8B / metabolism
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Signal Transduction / genetics
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Signal Transduction / immunology
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Spinal Cord / immunology
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Spinal Cord / pathology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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T-Lymphocytes / pathology
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T-Lymphocytes / transplantation
Substances
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Interleukin-17
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Mog protein, mouse
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Myelin Proteins
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Myelin-Associated Glycoprotein
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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Receptors, Interleukin-8B
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Interferon-gamma
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Granulocyte-Macrophage Colony-Stimulating Factor