Co-transfer of CD4+ and CD8+ T cells from NOD mice into Rag1−/− NOD mice upregulated the incidence of diabetes, whereas co-transfer of CD4+ and CD8+ T cells from IL-27rα−/− NOD mice into Rag1−/− NOD mice did not induce diabetes, demonstrating that IL-27 signaling is essential for T1D development (191). This evidence concerns the gene CD4 and type 1 diabetes mellitus.