Myelin oligodendrocyte glycoprotein-specific T and B cells cooperate to induce a Devic-like disease in mice.
Multiple sclerosis (MS) is a clinically and pathologically heterogeneous inflammatory/demyelinating disease of the CNS. In the MS variant Devic disease, lesions are predominantly found in the optic nerves and spinal cord but not the brain. The immunological bases of the different forms of MS are unknown. We previously generated myelin oligodendrocyte glycoprotein-specific (MOG-specific) TCR transgenic mice (TCRMOG mice; also referred to as 2D2 mice) and reported that a large proportion of these mice develop spontaneous isolated optic neuritis. We have now crossed the TCRMOG mice with MOG-specific Ig heavy-chain knock-in mice (IgHMOG mice; also referred to as Th mice), in which one-third of the B cells are specific for MOG. In these mice, MOG-specific B cells are very efficient in presenting MOG to the transgenic T cells and undergo class switching to IgG1 in the presence of the transgenic T cells. Sixty percent of TCRMOG x IgHMOG mice spontaneously developed a severe form of experimental autoimmune encephalomyelitis (EAE). Histological examination of the CNS revealed a selective distribution of meningeal and parenchymal inflammatory lesions in the spinal cord and optic nerves. Thus, CNS antigen-specific T and B cells cooperate to induce a distinct clinicopathologic EAE pattern that closely replicates human Devic disease.
Bettelli
Estelle
E
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Baeten
Dominique
D
Jäger
Anneli
A
Sobel
Raymond A
RA
Kuchroo
Vijay K
VK
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009471:Neuromyelitis Optica / Q000276:immunology*; D009900:Optic Nerve / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013116:Spinal Cord / Q000473:pathology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D007143:Immunoglobulin Heavy Chains; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011948:Receptors, Antigen, T-Cell