myelin-basic-protein and 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide-methiodide

This paper reports that DA rats develop experimental autoimmune encephalomyelitis (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 micrograms peptide + IFA induced EAE in DA rats. Lewis (LEW) rats did not develop EAE, even after immunization with 100 micrograms encephalitogenic peptide (MBP68-86) + IFA, but were rendered tolerant to EAE. DA rat T cells proliferated to peptide, and proliferation was inhibited 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 requirement for T cell costimulation through the B7/CD28 costimulatory pathway. The inhibitory effect of CTLA4Ig was abrogated in the presence of anti-TGF-beta-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 LEW rats (which did not develop EAE) failed to secrete these cytokines. Although this line did not express TNF-alpha or IL-10 mRNA, IFN-gamma mRNA was detected, suggesting posttranscriptional regulation of IFN-gamma expression. Attempts to induce unresponsiveness in DA rats with encephalitogenic peptide-coupled splenocytes were also unsuccessful.

Topics: Amino Acid Sequence; Animals; Cross-Linking Reagents; Cytokines; Encephalomyelitis, Autoimmune, Experimental; Ethyldimethylaminopropyl Carbodiimide; Female; Freund's Adjuvant; Immune Tolerance; Injections, Intravenous; Injections, Subcutaneous; Lipids; Lymphocyte Activation; Male; Molecular Sequence Data; Myelin Basic Protein; Peptide Fragments; Rats; Rats, Inbred Lew; Species Specificity; Spleen; T-Lymphocytes