CD4 and type 1 diabetes mellitus: Regulatory T cells (Tregs) express both CTLA-4 (96) and PD-1 (97), essential in their activation and suppressive role in peripheral immune tolerance (97, 98, 99) and a deficiency in the ability to upregulate PD-1 and efficiently use the PD-1/PD-L pathway has been observed in CD4+ CD25+ Tregs from T1D patients (100).