The magnitude and encephalogenic potential of autoimmune response to MOG is enhanced in MOG deficient mice.
Myelin oligodendrocyte glycoprotein (MOG) is a minor component of central nervous system myelin presumably implicated in the pathogenesis of Multiple Sclerosis (MS). Immunization with MOG leads to the development of Experimental Autoimmune Encephalomyelitis (EAE), the experimental model of MS. It has been suggested that its encephalitogenic potential may be due to the lack of MOG self-immune tolerance. To clarify this, we have generated a MOG deficient mouse (MOG(-/-)) strain. Surprisingly, MOG(35-55)specific proliferation and Th1-type cytokine production were markedly enhanced in MOG(-/-)mice compared to wild type control. Furthermore, adoptive transfer of MOG(35-55)specific T cells, isolated from MOG deficient mice, into wild-type recipients resulted in the development of a more severe disease, indicating a high capacity of MOG(-/-)T cells to initiate effector responses. Interestingly, T cell reactivity to overlapping MOG peptides in MOG(-/-)mice did not reveal new potential immunodominant epitopes in H-2(b)mice. Taken together, our data suggests that MOG self-tolerance modulates the encephalitogenic potential of autoreactive MOG T cells in the periphery.
Liñares
David
D
Department of Biochemistry, La Trobe University, Bundoora, Vic 3086, Australia.
Mañá
Paula
P
Goodyear
Melinda
M
Chow
Anne M
AM
Clavarino
Chelsea
C
Huntington
Nicholas D
ND
Barnett
Louise
L
Koentgen
Frank
F
Tomioka
Ryo
R
Bernard
Claude C A
CC
Freire-Garabal
Manuel
M
Reid
Hugh H
HH
D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology*; D017353:Gene Deletion; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000378:metabolism; D018992:Myelin-Associated Glycoprotein / Q000172:deficiency* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000737:chemistry; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; C571326:MOG protein, human; C571327:Mog protein, mouse; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein