SPINAL-CORD NEUROPATHOLOGY IN RAT EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS - MODULATION BY ORAL-ADMINISTRATION OF MYELIN BASIC-PROTEIN

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory dis ease of the central nervous system (CNS) in which clinical neurologica l signs and histopathologic changes of disease can be suppressed by fe eding CNS myelin proteins. Using immunohistochemistry and image analys is, the cellular immune response was quantified over the rostral-cauda l axis of the spinal cord in rats with EAE and in animals fed high-or low-dose myelin basic protein (MBP) prior to inducing EAE (tolerized a nimals). In a subset of rats, MBP was fed 9 days after MBP immunizatio n to examine the effect of oral tolerance on the progression of CNS pa thology. In unfed rats or rats fed vehicle only, activated microglia a nd macrophages were co-localized with T-lymphocytes throughout the spi nal cord, but greater cellular reactions were evident in gray matter r elative to white matter. In all tolerized animals, the CNS inflammator y response was reduced relative to controls. Subtle pathologic changes were occasionally observed in the CNS of MBP-fed animals, but the dis tribution of inflammatory cells in the dorso-ventral axis was more pol arized in animals fed high-dose MBP. In this group, more T-cells and a ctivated microglia were present in the dorsal spinal cord, specificall y in the gray matter In the group fed MBP after disease induction, cli nical disease progressed as in control non-fed rats, but recovery from disease appeared to be accelerated. Thus, the results presented here provide a comprehensive analysis of the distribution and magnitude of inflammatory cells within the spinal cord in EAE and challenge the the ory that MBP-induced EAE is only a white matter disease. These data al so describe how the activation and distribution of immune effector cel ls is altered by oral tolerance and may help predict a range of neurol ogical deficits not previously appreciated in EAE, particularly those effected by gray matter pathology.