Analysis of experimental autoimmune encephalomyelitis induced in F344 ratsby pertussis toxin administration

To elucidate the factor(s) accelerating the autoimmune disease processes, w e induced two types of experimental autoimmune encephalomyelitis (EAE), sev ere and very mild, in F344 rats by immunization with myelin basic protein ( MBP) plus pertussis toxin (PT) (PT+) or with MBP alone (PT-) and compared t he differences between the-two. Immunohistochemical examinations showed tha t although the nature of inflammation was essentially the same between the two groups, the proportion of V beta 8.2(+) T cells in the CNS lesion of PT (+) rats was larger than that of PT (-) rats. Cytokine analysis by competi tive PCR revealed that IL-10 mRNA in the lymphoid organ was significantly s uppressed in the PT(+) group, whereas levels of IFN-gamma,TNF-alpha and TGF -beta mRNA were insignificantly different after PT administration. In addit ion, T cells taken from PT (+) rats proliferated well in response to MBP wh ile those from PT (-) rats showed a marginal response to the same antigen. However, this finding does not indicate the switching of non-encephalitogen ic to encephalitogenic T cells upon PT administration because PT (-) rats c ontained encephalitogenic T cells and/or their precursor cells as revealed by adoptive transfer experiments. Taken together, these findings suggest;th at suppression of IL-10 by PT administration is the major factor contributi ng to the exacerbation of EAE in PT(+) rats. (C) 2000 Elsevier Science B.V. All rights reserved.