PD-1, Tim-3 and LAG-3 are co-inhibitory receptors that are critical for controlling autoimmunity: studies with blocking antibodies as well as gene-deficient mice demonstrated that these pathways, individually or synergistically, play important roles in type 1 diabetes and other autoimmune diseases [9, 11–13, 32]. This evidence concerns the gene HAVCR2 and type 1 diabetes mellitus.