CD4 and type 1 diabetes mellitus: As was the case for the TR1-like CD4+ T-cells induced by T1D-relevant pMHC class II-NPs in NOD mice1, the PDC-E2166–181/IAg7 tetramer+ T-cells that expanded in response to PDC-E2166–181/IAg7-NP treatment were CD25–/FoxP3– and expressed the TR1 markers lymphocyte-activation gene-3 (LAG-3), CD49b (integrin a2 or very-late antigen-2), LAP (transforming growth factor beta latency-associated peptide), program cell death protein-1 (PD1), and inducible T-cell costimulator (ICOS) (Fig. 1f and Supplementary Fig. 1a–c).