Induction of experimental autoimmune encephalomyelitis in transgenic mice expressing ovalbumin in oligodendrocytes.
We have used the 5' flanking sequence of the myelin basic protein gene known to include the core promoter and a strong oligodendrocyte (ODC)-specific enhancer to target expression of the well-studied model antigen ovalbumin (OVA) to ODC in transgenic mice. OVA protein was detected in a tissue- and cell-specific manner in these "ODC-OVA" mice. Without immunization, CD4 T cells and B cells remained ignorant of the neo-self antigen expressed in the central nervous system (CNS), as indicated by unimpaired development and lack of activation of OVA/IA(b)-specific TCR transgenic T cells in these mice, and the ability to mount normal OVA-specific recall and antibody responses. Upon immunization with OVA in complete Freund's adjuvant, about half of the transgenic mice developed neurological symptoms characteristic of experimental autoimmune encephalomyelitis (EAE). Mononuclear infiltrates in the brain and spinal cord contained both macrophages and T cells, similar to classical models of EAE induced by immunization with CNS antigens in adjuvant. The wealth of immunological reagents available to study and manipulate the OVA-specific response should make this new model useful for the investigation of components and mechanisms involved in CNS-specific autoimmunity.
Cao
Yi
Y
Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
Toben
Catherine
C
Na
Shin-Young
SY
Stark
Kirsten
K
Nitschke
Lars
L
Peterson
Alan
A
Gold
Ralf
R
Schimpl
Anneliese
A
Hünig
Thomas
T
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015153:Blotting, Western; D001921:Brain / Q000276:immunology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004742:Enhancer Elements, Genetic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology; D009836:Oligodendroglia / Q000276:immunology*; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology
D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin