title: Encephalitogenic T cells are present in Lewis rats protected from autoimmune encephalomyelitis by coimmunization with MBP73-84 and its analog.
abstract: Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) that is mediated by T helper 1 (Th1) CD4+ T cells. Lewis rats can be protected from actively induced EAE by coimmunization with the encephalitogenic myelin basic protein (MBP) epitope 73-84 and its single alanine-substituted analog 1028. Although analog 1028 cannot induce either active or passive EAE, it does elicit a Th1-like response that is cross-reactive with MBP73-84. Analog 1028 can effectively inhibit clinical EAE in a dose-dependent manner when rats are coimmunized with the encephalitogenic peptide MBP73-84 and 1028 in complete Freund adjuvant (CFA). Stimulation of cells from MBP73-84:1028-coimmunized protected rats proliferate and secrete interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in vitro in response to MBP73-84. Furthermore, coimmunized protected rats harbor a population of MBP73-84-reactive potentially encephalitogenic T cells, because splenocytes from these rats can be stimulated to transfer passive EAE to naive recipients. Thus, the protection of coimmunized rats by analog 1028 is not due to the inhibition of priming of MBP73-84-reactive T cells or alteration of the cytokine secretion profile of the MBP73-84-reactive cell population. Rather, MBP73-84-reactive potentially encephalitogenic T cells are primed in these protected animals.
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Stepaniak
authors.forename: K E
authors.initials: KE
authors.lastname: Gould
authors.forename: R H
authors.initials: RH
authors.lastname: Swanborg
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D006649:Histocompatibility Antigens / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D004676:Myelin Basic Protein / Q000276:immunology* / Q000494:pharmacology; D010446:Peptide Fragments / Q000276:immunology* / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006649:Histocompatibility Antigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma