Rapamycin Expands and Confers Resistance to Apoptosis of Human Inducible Regulatory T Cells (TRI)

The immunosuppressive drug Rapamycin (RAPA) has been shown to promote expansion of CD4+IL-10+ natural human regulatory T cells (nTreg) in vitro and in vivo. RAPA effects on inducible Treg (Tri) are unknown, and this study explores in vitro responses of Tr1 to this drug. CD4+CD25neg T cells isolated from PBMC of normal donors were used to generate Tr1 cells. Expanded Tr1 cells were tested for surface markers, expression of survival proteins, resistance to apoptosis and the ability to suppress proliferation of autologous CD4+CD25neg responder T cells (RC) in functional assays. RAPA was found to promote the generation of human Tr1 cells from autologous CD4+CD2Sneg precursors in peripheral blood. Tr1 cells + RAPA mediated higher suppression (p