title: Strain variation in autoimmunity: attempted tolerization of DA rats results in the induction of experimental autoimmune encephalomyelitis.
abstract: 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.
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Lenz
authors.forename: N A
authors.initials: NA
authors.lastname: Wolf
authors.forename: R H
authors.initials: RH
authors.lastname: Swanborg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003432:Cross-Linking Reagents; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D005022:Ethyldimethylaminopropyl Carbodiimide / Q000031:analogs & derivatives; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007108:Immune Tolerance; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008055:Lipids; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D003432:Cross-Linking Reagents; D016207:Cytokines; D008055:Lipids; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C114843:incomplete Freund's adjuvant; C110235:myelin basic protein 68-86; C041829:1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide methiodide; D005620:Freund's Adjuvant; D005022:Ethyldimethylaminopropyl Carbodiimide