CD4 and type 1 diabetes mellitus: CD4+ expression of PD-1 was reduced in T1D patients, and CD4+ CD25+ T reg cells of patients with T1D have impaired upregulation of PD-1 in response to stimulation in comparison to normal controls, suggestive of a role for PD-1 in defective immune regulation even in traditional T1D pathogenesis (67–69).