We evaluated the role of the costimulatory molecule 87-l in overcoming perlpheral Ignorance in transgenic mice, which expressed the glycoprotein(GP) or nucleoproteln (NP) of lymphocytic choriomeningltls virus (LCMV) as the self-antigen in pancreatic j3 cells. The viral transgenes or 87-l alone did not induce autoimmune diabetes (IDDM). However, in blgenic mice expressing 87-l and LCMV-GP, anti-self (viral) cytotoxic T lymphocytes (CTL) were activated without viral infection and spontaneous IDDM occurred. In contrast, bigenic RIP-B7-1 x RIP-NP mice with thymlc expression of the self (viral-NP) antlgen deleted the majority of their autoreactlve CTL and did not develop spontaneous IDDM. However, these mice developed fastonset IDDM 14 days after LCMV infection, whereassingle-transgenlc RIP-NP llttermates developed IDDM only within 4-5 months. Rapid IDDM was associated with Increased numbers of ant&elf CTL and a predominance of IFNy produced by islet-inflltratlng lymphocytes, whereas single transgenic RIP-NP littermates with slow-onset IDDM displayed less anti-self CTL and more IL+ and IL-lO-producing T lymphocytes in pancreatic infiltrates.