CD4 and type 1 diabetes mellitus: Hunter et al. posited that the lack of protection in NOD-Idd3/Idd5.1 mice may result from T1D resistance alleles at Idd3 increasing the expression of CTLA-4 on the surface of CD4+ and CD8+ T cells that may render higher levels of inhibitory ligand-independent CTLA-4 induced by protective alleles at Idd5.1/Ctla-4 somewhat redundant (41, 53).