CD4 and diabetes mellitus: Although CD4+ T cells are essential for the triggering and progression of diabetes, T1D development requires important contributions from cytotoxic CD8+ T cells that destroy β cells of the islets of Langerhans, leading to insufficiency of circulating insulin in NOD mice (Lieberman et al., 2003; Verdaguer et al., 1997; Trudeau et al., 2003).