Genetic and epigenetic influence on EAE phenotypes induced with different encephalitogenic peptides.
Different encephalitogenic peptides can induce two distinct experimental autoimmune encephalomyelitis (EAE) phenotypes in different mouse strains. To determine whether different peptides induce distinct phenotypes in genetically identical mice, parental strain and (SJLXC3H/HeJ)F1 mice were sensitized with myelin proteolipid protein peptide p139-151 or p215-232. p139-151 was non-encephalitogenic in C3H/HeJ mice and p215-232 was non-encephalitogenic in SJL mice. p139-151 induced typical acute EAE in SJL and F1 mice with most CNS inflammatory/demyelinating lesions located in the spinal cord. p215-232 induced mild clinical disease in only two of 10 C3H/HeJ mice; in 11 of 13 F1 mice (85%) it induced a disease spectrum that included typical paralytic acute EAE with a predominance of spinal cord lesions and later-onset mild EAE with predominance of brain stem/cerebellar lesions. Thus, the EAE phenotype induced in F1 mice by one encephalitogen, e.g. p139-151, can be the same as that induced in the susceptible parent. However, other encephalitogenic peptides, e.g. p215-232, may induce a broad range of heterogeneous EAE phenotypes in syngeneic mice. These data indicate that in some encephalitogenic responses, epigenetic factors influence EAE incidence, time of onset, severity, neurological signs and CNS lesion distribution.
Sobel
R A
RA
Pathology and Laboratory Services (113), Palo Alto Veterans Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, USA. raysobel@leland.stanford.edu
D000208:Acute Disease; D000818:Animals; D000941:Antigens / Q000276:immunology; D001933:Brain Stem / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D005260:Female; D005838:Genotype; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D010243:Paralysis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology*; D010641:Phenotype; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology
D000941:Antigens; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); C412082:myelin proteolipid protein (215-232)