In the present study, we demonstrate that the highly specific TYK2 pseudokinase inhibitors, BMS-986165 and BMS-986202, modulate three critical nodes in T1D pathophysiology including: 1) immune cell activation and target tissue infiltration; 2) β cell inflammation and survival; and 3) direct interaction of β cells with antigen-specific CD8+ T cells. Here, CD8A is linked to type 1 diabetes mellitus.