Epitope spread is not critical for the relapse and progression of MOG 8-21 induced EAE in Biozzi ABH mice.
Emerging autoimmunity (epitope-spreading) generated as a consequence of myelin damage is suggested to underlie the relapses in multiple sclerosis (MS). Myelin oligodendrocyte glycoprotein (MOG 8-21) induces relapsing EAE in ABH mice characterized by broadening of the autoimmune reportoire. Despite epitope spreading tolerance to the priming antigen, but not emerging epitope reactivities, resulted in long-term inhibition of clinical relapse. In contrast, spinal cord homogenate induced EAE was dominated by a proteolipid protein (PLP 56-70) autoreactivity despite the plethora of CNS antigens in the immunogen. This data suggests that during relapsing-remitting demyelinating disease the pathogenic process is dominated by the initiating antigen, with only a minor role played by emerging T-cell populations. These findings may have important implications for the efficacy of antigen-based immune therapies in autoimmune disorders.
Smith
Paul A
PA
Department of Immunobiology, Biomedical Primate Research Centre, Lange Kleiweg 139, 2280 GH, Rijswijk, The Netherlands.
Morris-Downes
Margaret
M
Heijmans
Nicole
N
Pryce
Gareth
G
Arter
Elizabeth
E
O'Neill
Janet K
JK
't Hart
Bert
B
Baker
David
D
Amor
Sandra
S
D000818:Animals; D001059:Apoproteins / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D000939:Epitopes / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D038602:Mice, Biozzi; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein / Q000633:toxicity; D018992:Myelin-Associated Glycoprotein / Q000633:toxicity*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000633:toxicity; D012008:Recurrence; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D001059:Apoproteins; D016207:Cytokines; D000939:Epitopes; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments