Distinct immune regulation of the response to H-2b restricted epitope of MOG causes relapsing-remitting EAE in H-2b/s mice.
To find immune mechanisms underlying relapse regulation, we developed a model of relapsing-remitting experimental autoimmune encephalomyelitis (EAE) in (B6xSJL) F1 (H-2(b/s)) mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG(35-55)) and compared with low/non-relapsing B6 (H-2(b)) mice. In relapsing H-2(b/s) mice, inflammatory lesions scattered throughout the white matter with extensive demyelination, consisted of CD4(+) T and B220(+) B cells with fewer Mac3(+) macrophages. Memory T cell proliferation to MOG(35-55) was significantly enhanced. Switch of macrophage chemoattractant protein-1 (MCP-1) production from GFAP(+) astrocytes to CD3(+) T cells was observed. Distinct patterns of inflammation and demyelination, MOG(35-55) memory T cell response and regulation of MCP-1 are associated with relapsing H-2(b/s) phenotype.
Skundric
Dusanka S
DS
Department of Neurology, Division of Neuroimmunology, Wayne State University School of Medicine, 421 E Canfield, 3141 Elliman Building, Detroit, MI 48201, USA. skundric@cmb.biosci.wayne.edu
Zakarian
Vaagn
V
Dai
Rujuan
R
Lisak
Robert P
RP
Tse
Harley Y
HY
James
Jascinth
J
D000818:Animals; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018932:Chemokine CCL2 / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000503:physiopathology; D000939:Epitopes / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology* / Q000494:pharmacology; D006183:H-2 Antigens / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology / Q000503:physiopathology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009413:Nerve Fibers, Myelinated / Q000276:immunology* / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology* / Q000494:pharmacology; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000943:Antigens, Differentiation; D015704:CD4 Antigens; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D000939:Epitopes; D006023:Glycoproteins; D006183:H-2 Antigens; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; C036763:monocyte-macrophage differentiation antigen; C445081:myelin oligodendrocyte glycoprotein (35-55)