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 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.
Lenz
D C
DC
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Wolf
N A
NA
Swanborg
R H
RH
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
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