Thalidomide and its analogs help with the co-stimulation of T-cells through the B7-CD28 complex by phosphorylating tyrosine on the CD28 receptor. In vitro data suggests this co-stimulation leads to increased Th1 type cytokine release of IFN-γ and IL-2 that further stimulates clonal T cell proliferation and natural killer cell proliferation and activity. This enhances natural and antibody dependent cellular cytotoxicity. Lenalidomide and pomalidomide are about 100-1000 times more potent in stimulating T-cell clonal proliferation than thalidomide. In addition, in vitro data suggests pomalidomide reverts Th2 cells into Th1 by enhancing transcription factor T-bet.