Experimental autoimmune meningitis: A novel neurological disease in CD28-deficient mice

C57BL/6 mice develop T-cell-mediated experimental autoimmune encephalomyeli tis (EAE) after immunization with the neuroantigen myelin oligodendrocyte g lycoprotein. (MOG). We immunized CD28-deficient C57BL/6 mice to determine t he role of T cell costimulation in the immune response to MOG. CD28(-/-) mi ce developed experimental autoimmune meningitis (EAM). EAM is a fatal, acut e 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 m ediated by CD4(+) T cells since CD4 depletion prevented the disease. Upon r echallenge, mice in which EAM was prevented by CD4(+) cell depletion develo ped 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 asepti c meningitis. (C) 1999 Academic Press.