title: T cell vaccination against autoimmune diabetes in nonobese diabetic mice.
abstract: The diabetogenic autoimmune process was accelerated in 23 days nonirradiated postnatal nonobese diabetic (NOD) female mice by adoptive transfer of pathogenic, polyclonal CD4+ 8- T cells isolated from diabetic spleens. Recipient mice developed hyperglycemia 15 days after transfer of pathogenic immune cells with typical histological signs of pancreatic infiltration. The CD4+V beta 8+ T cells isolated from diabetic spleens and activated by surface-immobilized anti-TCRV beta 8 monoclonal antibody (mAb, clone F23.1) induced suppression of a diabetogenic disease process accelerated earlier by adoptively transferred polyclonal CD4+8- T cells. When CD4+V beta 8+ T cells isolated from diabetic spleens were activated by cross-linking TCRV beta 8 and systemically injected into young female NOD mice, an endogenous immunosuppressive circuit was stimulated that completely prevented development of insulitis and disease. A suppressor mechanism involving CD8+ T cells might be involved since in vitro these cells strongly proliferated in response to irradiated CD4+ V beta 8+ T cells that in blocking experiments with specific mAb was found to be class I major histocompatibility complex (MHC)-restricted. Hence, T cells expressing the CD8 phenotype specifically respond to idiotypic or ergotypic determinants on the inducing activated CD4+V beta 8+ T cells and effectively suppress a diabetogenic disease process by a mechanism that may involve T-T cell interactions.
authors.affiliation: Sansum Medical Research Foundation, Laboratory of Immunology, Santa Barbara, CA 93105.
authors.forename: B
authors.initials: B
authors.lastname: Formby
authors.forename: T
authors.initials: T
authors.lastname: Shao
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001327:Autoimmune Diseases / Q000517:prevention & control*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control*; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014611:Vaccination
chemical_list: D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell