Autoimmunity Without Diabetes in Transgenic Mice Expressing β Cell-Specific CD86, But Not CD80: Parameters that Trigger Progression to Diabetes

Abstract

To define more clearly the roles of CD80 (RIP-CD80) and CD86 (RIP-CD86) in the activation of autoreactive T cells in vivo, we generated transgenic mice expressing either or both costimulatory molecules on the β cells of the pancreas. While RIP-CD80 mice do not show any sign of autoimmunity, at the age of 7 mo RIP-CD86 transgenic mice develop a lymphoid infiltrate with both IFN-γ- and IL-4-positive cells in the vicinity of the islets; these mice, however, never progress to diabetes. This fundamental difference in the ability of CD80 and CD86 to activate self-reactive T cells in vivo is, however, obliterated when the level of TCR signaling is increased by either TNF-α or transgenic MHC class II expression. These results support the suggestion that CD80 and CD86 mainly differ at the level of the intensity of the signals they deliver.