None of the 287 NOD mice treated with second-generation CD28-CAR and 4-1BB-CAR CD8+ T cells targeting the I-Ag7-B:9-23(R3) complex developed T1DM before 18 weeks of age; however, protection declined over time, indicating that these CAR-T cells can only delay, but not prevent, the development of T1D (78). This evidence concerns the gene CD8A and type 1 diabetes mellitus.