RELAPSING AND REMITTING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS - A FOCUSED RESPONSE TO THE ENCEPHALITOGENIC PEPTIDE RATHER THAN EPITOPE SPREAD

The progression of experimental allergic encephalomyelitis (EAE) in ce rtain mouse strains has been reported to involve a broadening of the r esponse to myelin antigens, apparently resulting from priming to endog enous determinants of the myelin sheath. The phenomenon has been terme d determinant spread. Interest in this effect has centered on the mech anism it offers to explain the progressive, relapsing and remitting co urse of EAE and indeed of multiple sclerosis. We have conducted a syst ematic, longitudinal study in SJL mice to look for determinant spread during relapsing and remitting EAE, correlating epitope recognition an d cytokine production with disease severity. Disease was induced using three of the four encephalitogenic proteolipid protein or myelin basi c protein epitopes, and responses to each of four epitopes recognized by SJL T cells were tracked through acute disease, remission and relap se. The responses of lymph node cells, splenocytes and central nervous system (CNS)-infiltrating T cells were analyzed. While marginal, tran sient responses to secondary epitopes were detectable in splenocytes, CNS-infiltrating cells showed a dominant response to the original dise ase-inducing epitope without evidence of a shift to other determinants during relapse. Disease relapse was correlated with an increase in CN S-infiltrating cells and a high proliferative and interferon (IFN)-gam ma response to the disease-inducing peptide. During remission, there w as a decrease in numbers of cells infiltrating the CNS. These cells we re downregulated, showing low if any response to the myelin peptides t ested as measured by proliferation, production of IFN-gamma or product ion of IL-4. Our findings argue strongly against a causal role for det erminant spread in disease relapse as observed in these models of EAE.