T cell vaccination against autoimmune diabetes in nonobese diabetic mice.
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.
Formby
B
B
Sansum Medical Research Foundation, Laboratory of Immunology, Santa Barbara, CA 93105.
Shao
T
T
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
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D011948:Receptors, Antigen, T-Cell