Regarding heterogeneous CD3-CD4+ cells from the “large gate” that expressed PD-1 (Fig 1 panel E), subjects with T1D did not upregulate PD-1 in culture, in contrast to CD and CTRL, which increased PD-1 expression despite the lack of T-cell receptor, suggesting a bystander effect of anti-CD3/anti-CD28 stimulation on these cells. Here, CD28 is linked to type 1 diabetes mellitus.