Vav1-deficient mice are resistant to MOG-induced experimental autoimmune encephalomyelitis due to impaired antigen priming.
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.
Korn
Thomas
T
Department of Neurology, Neuroimmunology Branch and MS Clinical Research Group, Bayerische Julius-Maximilians-Universität Würzburg, Würzburg, Germany. netkor@uniklinik-saarland.de
Fischer
Klaus-Dieter
KD
Girkontaite
Irena
I
Köllner
Gabriele
G
Toyka
Klaus
K
Jung
Stefan
S
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics*; D018797:Cell Cycle Proteins; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D007111:Immunity, Cellular / Q000187:drug effects / Q000235:genetics; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics; D051567:Proto-Oncogene Proteins c-vav; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
D018797:Cell Cycle Proteins; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; C496619:Vav1 protein, mouse