GENETIC INFLUENCE ON DISEASE COURSE AND CYTOKINE RESPONSE IN RELAPSING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

A protracted and relapsing form of experimental allergic encephalomyel itis (EAE) develops in the DA rat after immunization with rat spinal c ord homogenate (SCH) emulsified in incomplete Freund's adjuvant (IFA), The genetic influence on this model has been analyzed by immunizing M HC congenic strains on both LEW and DA genetic backgrounds, and recomb inant inbred strains between DA and E3 rats, An in situ hybridization assay was used to examine the expression of mRNA for IFN-gamma, IL-4, IL-10 and transforming growth factor (TGF)-beta both in sections of sp inal cords and the antigen-induced expression for these cytokines by s plenocytes after in vitro stimulation with encephalitogenic MBP peptid es, The susceptibility of relapsing EAE after immunization with SCH in IFA in the DA strain, but not the E3 strain, was correlated with a la ck of expression for TGF-beta in the spinal cord, The recombinant inbr ed DXEB rats developed a severe EAE while surprisingly no signs of dis ease were observed in the DXEA strain, which shares the MHC region wit h the DXEB strain, after immunization with the MBP 63-87 peptide, Resi stance to relapsing EAE in the DXEA strain correlated with increased n on-MHC controlled expression for TGF-beta and lack of IFN-gamma in the spinal cord, The same pattern of cytokine expression was seen in sple nocytes after stimulation in vitro with the MBP 63-87 peptide. A sprea ding of the immune response to the MBP 87-110 peptide was seen, Non-MH C genes controlled the quality of this response: splenocytes from MBP 63-87 immunized DXEB rats responded in vitro towards the MBP 87-110 pe ptide by expressing mRNA for IFN-gamma, IL-10 and IL-4, whereas in the DXEA strain the corresponding response involved IL-4 and TGF-beta, Ta ken together these data show that non-MHC controlled expression of mRN A for TGF-beta is associated with resistance to EAE.