CTLA4 and type 1 diabetes mellitus: Regulatory T cells (Tregs) express both CTLA-4 (101) and PD-1 (102), which are essential in their activation and suppressive role in peripheral immune tolerance (103), and a deficiency in the ability of Tregs to up-regulate PD-1 and efficiently use the PD-1/PD-L pathway has been observed in patients with T1DM (104).