IFN-gamma plays a critical down-regulatory role in the induction and effector phase of myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis.
129/Sv mice are resistant to induction of experimental autoimmune encephalomyelitis (EAE) induced with myelin oligodendrocyte glycoprotein peptide (MOG35-55). Mice of this strain lacking the gene coding for the ligand-binding chain of the IFN-gamma receptor develop EAE with high morbidity and mortality. Spleen cells from sensitized IFN-gammaR-/- mice proliferated extensively when stimulated with MOG peptide in culture and produced high levels of IFN-gamma and TNF but no detectable IL-4. Transfer of spleen cells from sensitized IFN-gammaR-/- mice produced EAE in both IFN-gammaR+/+ and IFN-gammaR-/- recipients. Disease was severe in IFN-gammaR-/- recipients and mortality high (77%). Surviving mice remained moribund until termination of the experiments. IFN-gammaR+/+ recipients developed disease of equal severity, but with no mortality, and recovered significantly. These results indicate that IFN-gamma is not essential for the generation or function of anti-MOG35-55 effector cells but does play an important role in down-regulating EAE at both the effector and induction phase of disease.
Willenborg
D O
DO
Neuroscience Research Unit, The Canberra Hospital, Australia. David.Willenborg@anu.edu.au
Fordham
S
S
Bernard
C C
CC
Cowden
W B
WB
Ramshaw
I A
IA
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000954:Antigens, Surface; D001323:Autoantibodies / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000235:genetics / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology; D013154:Spleen / Q000276:immunology; D000096743:Interferon gamma Receptor
D015703:Antigens, CD; D000954:Antigens, Surface; D001323:Autoantibodies; D016207:Cytokines; D007371:Interferon-gamma; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C571327:Mog protein, mouse