Inflammatory central nervous system disease in lupus-prone MRL/lpr mice: comparative histologic and immunohistochemical findings.
The brains of pathogen-free autoimmune MRL/lpr, NZBWF1 and NZB mice were examined for central nervous system (CNS) inflammation in premoribund 8-week-old animals and at ages when active systemic lupus erythematosus (SLE) was present. CNS inflammation was observed only in MRL/lpr mice. Immunohistochemical studies of brains from young MRL/lpr mice found that infiltrates were composed primarily of CD4+ cells. Older MRL/lpr mice (22 and 26 weeks of age) had CD4+ cells predominantly, but CD8+ and B220+ cells were also present. Perivascular leakage of IgG was a prominent and unexpected finding in the MRL/lpr model. Congenic MRL/+ mice with late-onset autoimmunity had no inflammatory cells in brain tissue, and there was no perivascular staining with IgG or albumin. Our findings suggest that MRL/lpr mice are a useful model for studies of lupus-associated CNS inflammatory disease, and perivascular leakage may be a primary mechanism for entry of IgG into the brain.
Vogelweid
C M
CM
Department of Pathology, College of Veterinary Medicine, University of Missouri, Columbia 65212.
Johnson
G C
GC
Besch-Williford
C L
CL
Basler
J
J
Walker
S E
SE
D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001927:Brain Diseases / Q000378:metabolism / Q000473:pathology*; D015704:CD4 Antigens / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008817:Mice, Mutant Strains; D009443:Neuritis / Q000378:metabolism / Q000473:pathology*
D015704:CD4 Antigens; D007074:Immunoglobulin G