CD4 and type 1 diabetes mellitus: Additional examples of pathogenic mechanisms shared between NOD mice and T1D-susceptible humans are alterations in the T cell–inhibitory cytotoxic T lymphocyte-associated-4 (CTLA-4) pathway (43) and diminished function of CD4+CD25+ regulatory T cells, essential for peripheral tolerance, due to gene variants affecting interleukin 2 signaling (44, 45, 46).