Dasatinib inhibits in vivo T-cell proliferation and in combination with cyclosporine A or rapamycin leads to enhanced inhibition of T-cell proliferation in vitro. (A) PBMCs were loaded with CFSE and stimulated with OKT3 (100 ng/mL) in the presence or absence of dasatinib (1 nM), cyclosporine A (CsA; 10 ng/mL [8.3 nM]), or rapamycin (0.1 ng/mL [0.11 nM]). Proliferating T cells were analyzed after 120 hours. Data from 2 representative donors are shown to illustrate moderate interindividual differences in response to each drug. The percentage of proliferating T cells is indicated in each panel. (B) PBMCs were loaded with CFSE and stimulated with OKT3 (100 ng/mL) in the presence or absence of dasatinib (1 or 2 nM), or rapamycin (0.1 or 0.2 ng/mL). Proliferating T cells were analyzed after 120 hours. (C) Spleen and lymph nodes cell from C57BL/6 mice and loaded with CFSE and adoptively transferred by tail vein injection to lethally irradiated C3H/HeJ recipient mice (40 × 10⁶ cells per recipient; n = 3 mice/group). Lethally irradiated C57BL/6 recipient mice were used as syngeneic controls. Compounds were administered by oral gavage once per day at the doses indicated in a vehicle consisting of 50% propylene glycol and 50% water. Lymphocytes were harvested from the spleens of recipient mice on day 3 after transfer and analyzed by flow cytometry for the CFSE content of the donor CD4⁺ lymphocytes. The response index relative to the syngeneic control group is indicated. Comparison of compound treated groups' response index to the vehicle-treated group was performed by Student t test (**P < .01). Error bars represent SEM.