P0(106-125) is a neuritogenic epitope of the peripheral myelin protein P0 and induces autoimmune neuritis in C57BL/6 mice.
The present study describes a new model of autoimmune neuritis in C57BL/6 mice induced by immunization with the novel neuritogenic epitope P0(106-125), derived from mouse peripheral myelin protein P0. Immunization with this peptide in combination with pertussis toxin induced high levels of peptide-specific CD4+ T cells in spleen and popliteal lymph nodes. Clinical symptoms of autoimmune neuritis started with a flaccid tail at day 10 postimmunization (p.i.), progressed to moderate paraparesis at day 15 p.i., declining thereafter with undetectable symptoms at day 40 p.i. Clinical disease activity paralleled decreased sciatic nerve motor conduction and histopathologic alterations of sciatic nerves. These included inflammatory infiltrates, mainly consisting of inducible nitric oxide synthase (iNOS)+ macrophages and CD4+ T cells. These data fit into the pathogenetic concept of murine autoimmune neuritis as a CD4+ TH1 cell-mediated disease. Our new mouse model provides an attractive tool to identify critical factors that regulate the severity of autoimmune responses in the peripheral nervous system.
Miletic
Hrvoje
H
Abteilung für Neuropathologie, Universität zu Köln, Germany.
Utermöhlen
Olaf
O
Wedekind
Christoph
C
Hermann
Manuel
M
Stenzel
Werner
W
Lassmann
Hans
H
Schlüter
Dirk
D
Deckert
Martina
M
D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D007279:Injections, Subcutaneous; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018993:Myelin P0 Protein / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D009444:Neuritis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D018993:Myelin P0 Protein; D010446:Peptide Fragments