Experimental autoimmune meningitis: a novel neurological disease in CD28-deficient mice.
C57BL/6 mice develop T-cell-mediated experimental autoimmune encephalomyelitis (EAE) after immunization with the neuroantigen myelin oligodendrocyte glycoprotein. (MOG). We immunized CD28-deficient C57BL/6 mice to determine the role of T cell costimulation in the immune response to MOG. CD28-/- mice developed experimental autoimmune meningitis (EAM). EAM is a fatal, acute disease characterized by simultaneous weakness in all limbs, photophobia, irritability, and spatial disorientation. Histologically, EAM consisted of an infiltrate of myeloid, monocytic, and lymphocytic leukocytes within the leptomeninges. In contrast, the brain parenchyma was unaffected. EAM was mediated by CD4+ T cells since CD4 depletion prevented the disease. Upon rechallenge, mice in which EAM was prevented by CD4+ cell depletion developed EAE not EAM. Therefore, the presence or absence of CD28 determines the initial phenotype of the immune response to MOG. EAM, which develops in the absence of CD28, is a unique experimental model for immune-mediated aseptic meningitis.
Perrin
P J
PJ
Department of Medicine, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Lavi
E
E
Rumbley
C A
CA
Zekavat
S A
SA
Phillips
S M
SM
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000737:chemistry; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology / Q000473:pathology; D005260:Female; D006098:Granulocytes / Q000276:immunology; D007114:Immunization; D008297:Male; D008582:Meningitis, Aseptic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein
D001324:Autoantigens; D018106:CD28 Antigens; D018925:Chemokines; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein