Induction of experimental allergic neuritis in the BN rat: P2 protein-specific T cells overcome resistance to actively induced disease.
T lymphocyte lines specific for the peripheral nerve myelin protein P2 were selected from the lymph nodes of Brown Norway (BN) rats immunized with bovine P2 protein in complete Freund's adjuvant. These T cells expressed the W3/25+, OX8-phenotype and responded specifically to bovine P2 protein, but not to PPD or bovine basic protein, in T cell proliferation assays. When injected i.v. into syngeneic recipients, BN P2-specific T cell lines induced both clinical and histologic signs of experimental allergic neuritis (EAN), overcoming the resistance of this rat strain to actively induced EAN. Although the histopathology of the disease was indistinguishable from that seen in T cell-mediated EAN in the Lewis rat, disease onset was considerably later, 7 to 8 days after cell transfer, as opposed to 4 days in Lewis. This lag phase between inoculation and disease onset could not be further reduced even by raising the cell dose to 50 X 10(6) cells/host. The fine specificity of the T cell response to P2 differs between Lewis- and BN-derived T cell lines. At least one neuritogenic epitope for each strain was present in the cyanogen bromide-derived peptide CB2 (residues 21-113), as shown by the ability of CB2-specific T cell lines derived from each strain to transfer EAN to the appropriate host strain. However, neuritogenic BN T lines fail to mount a response to the sequence 53-78 (SP4), which encompasses an epitope that is neuritogenic for Lewis rats. These results demonstrate that the resistance of BN rats to actively induced EAN is not due to the lack of appropriate P2-specific autoreactive T cell clones in the normal T repertoire. Furthermore, the results suggest that two distinct epitopes of P2 are responsible for EAN in Lewis and BN rats.
D000818:Animals; D002460:Cell Line; D000939:Epitopes / Q000276:immunology; D007113:Immunity, Innate; D007114:Immunization; D007116:Immunization, Passive; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology*; D018996:Myelin P2 Protein; D009444:Neuritis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D051381:Rats; D011914:Rats, Inbred BN / Q000276:immunology*; D011917:Rats, Inbred Lew / Q000276:immunology*; D011919:Rats, Inbred Strains / Q000276:immunology*; D013127:Spinal Nerves / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
D000939:Epitopes; D004676:Myelin Basic Protein; D018996:Myelin P2 Protein