Transgenic β-cell expression of CD80 does not require CD4+ T cell participation for β-cell destruction as diabetes-susceptible mice engineered to express the co-stimulatory molecule CD80 under control of the rat insulin promoter (RIP) within pancreatic β-cells (C57BL/6.RIP-B7.1 mice) develop disease in the absence of human or murine MHC-II, emphasizing the limitations of these artificial models (239). This evidence concerns the gene CD4 and diabetes mellitus.