Strain variation in autoimmunity: Attempted tolerization of DA rats results in the induction of experimental autoimmune encephalomyelitis

This paper reports that DA rats develop experimental autoimmune encephalomy elitis (EAE) when immunized with encephalitogenic myelin basic protein (MBP ) peptide (MBP63-81) in IFA, In contrast, most rodent strains are tolerized by this procedure. Doses as low as 5 mu g peptide + IFA induced EAE in DA rats. Lewis (LEW) rats did not develop EAE, even after immunization with 10 0 mu g encephalitogenic peptide (MBP68-86) + IFA, but were rendered toleran t to EAE, DA rat T cells proliferated to peptide, and proliferation was inh ibited by CTLA4Ig and by anti-B7.1 and anti-B7.2 mAbs, This indicates that the ease of induction of EAE in this strain does not reflect a decreased re quirement for T cell costimulation through the B7/CD28 costimulatory pathwa y. The inhibitory effect of CTLA4Ig was abrogated in the presence of anti-T GP-P-neutralizing Ab, An encephalitogenic DA T cell line expressed mRNA for the Th1 cytokines IFN-gamma and TNF-alpha, as well as IL-10, and secreted these cytokines, In contrast, a T cell line from peptide + IFA-immunized LE W rats (which did not develop EAE) failed to secrete these cytokines, Altho ugh this line did not express TNF-alpha or IL-10 mRNA, IFN-gamma mRNA was d etected, suggesting posttranscriptional regulation of IFN-gamma expression. Attempts to induce unresponsiveness in DA rats with encephalitogenic pepti de-coupled splenocytes were also unsuccessful.