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.