title: Induction of tolerance by T-cell vaccination is possible beyond the area of autoimmunity: down-regulation of immunity directed to foreign protein antigens.
abstract: T-cell vaccination using antigen-specific lines or clones has been shown to be effective in down-regulating immunity in various experimental autoimmune models. Anti-idiotypic networks developing during differentiation of the immune system are considered to be a safeguard against autoimmunity and these pre-existing networks are supposed to be a prerequisite for successful vaccination. However, the interesting question of feasibility of T-cell vaccination beyond the area of autoimmunity remains to be answered. The present study is the first one providing evidence of successful T-cell vaccination in mice immunized against foreign protein antigens (in this system supposedly no pre-existing network exists). Intraperitoneal (i.p.) administration of hen egg lysozyme (HEL)- and chicken egg albumin (OVA)-specific lymph node cells (LNC) were shown to effectively down-regulate immunity (as measured in a delayed type of hypersensitivity) to HEL and OVA, respectively. In contrast, vaccination was unsuccessful with methylated bovine serum albumin (mBSA)-specific LNC in mBSA immunity. Suppression induced by HEL- and OVA-specific LNC was antigen specific. Unlike the greater part of other studies, in which antigen-specific lines or clones were used, we used draining LNC of immunized mice, which after activation were fixed with glutardialdehyde and injected i.p. 10 days before immunization. Finally, effects of T-cell vaccination were studied in a chronic HEL-induced arthritis. Joint swelling, cell influx and cartilage matrix depletion were significantly less in mice treated with antigen-specific cells. We conclude that successful vaccination is feasible in mice rendered immune to foreign protein antigens using a pool of LNC as source of vaccine, suggesting no necessity of a strong pre-existing network.
authors.affiliation: Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: Jacobs
authors.forename: A E
authors.initials: AE
authors.lastname: van den Hoek
authors.forename: L B
authors.initials: LB
authors.lastname: van de Putte
authors.forename: W B
authors.initials: WB
authors.lastname: van den Berg
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D001168:Arthritis / Q000517:prevention & control; D002908:Chronic Disease; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011506:Proteins / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
chemical_list: D000941:Antigens; D011506:Proteins; D012710:Serum Albumin, Bovine; D010047:Ovalbumin; D009113:Muramidase