Moreover, rapamycin monotherapy already affected human CD4+CD25+FOXP3+ Treg function directly in vivo as nTreg isolated from T1D patients under rapamycin treatment had an increased capability to suppress proliferation of CD4+CD25− effector T-cells compared with that before treatment, without inducing alterations in the frequency of circulating nTreg and proliferation and cytokine production (62). This evidence concerns the gene CD4 and type 1 diabetes mellitus.