Abstract
Mice that lack the guanine nucleotide exchange factor (GEF) Vav1 exhibit particular defects in antigen-triggered T cell activation but may have an autoreactive T cell repertoire due to impaired intra-thymic negative selection. MOG(35-55)-induced experimental autoimmune encephalomyelitis (EAE) was used to test the susceptibility of Vav1(-/-) mice to organ-specific autoimmunity. Vav1(-/-) animals were found to be resistant to MOG(35-55)-EAE since the priming and in vivo expansion of myelin oligodendrocyte glycoprotein (MOG)-specific T cells was inefficient despite fully functional antigen presentation. Protection from cell-mediated autoimmunity was not due to a Th2 bias, to the lack of IL-2 or a failure of Vav1(-/-) T cells in terms of chemotactic mobility.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation / drug effects
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Antigen Presentation / genetics*
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Cell Cycle Proteins*
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Chemotaxis, Leukocyte / drug effects
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Chemotaxis, Leukocyte / genetics
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Disease Models, Animal
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Encephalomyelitis, Autoimmune, Experimental / genetics*
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / metabolism
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Female
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Genetic Predisposition to Disease / genetics*
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Immunity, Cellular / drug effects
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Immunity, Cellular / genetics
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Immunity, Innate / drug effects
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Immunity, Innate / genetics*
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / genetics
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Male
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Mice
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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-Associated Glycoprotein / pharmacology*
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments / pharmacology
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Proto-Oncogene Proteins / deficiency*
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins c-vav
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Signal Transduction / drug effects
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Signal Transduction / genetics
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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Th2 Cells / drug effects
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Th2 Cells / immunology
Substances
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Cell Cycle Proteins
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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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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-vav
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Vav1 protein, mouse