Figure 3. Effect of Belatacept and Mycophenolic Acid combinations on lymphoproliferation and Treg generation in MLR.

Since BEL is used clinically in combination with MPA (the in vivo active form of MMF), MLRs were also performed in presence of combinations of these drugs. Both flow ³H-TdR uptake assays and flow cytometric analysis were performed, the latter as described in Figures 1 and 2, with serial dilutions of MPA as indicated on the horizontal axis and with 0.1μg/ml or 1μg/ml concentrations of BEL. (n=3). MPA increased the generation of Tregs at sub-therapeutic concentrations, while inhibiting lymphoproliferation (top blue line with no BEL) (p<0.05). BEL, however, not only inhibited lymphoproliferation and Treg generation (points at 0 MPA) as described in Figure 2, but also abrogated the enhancement of Treg generation observed at low concentrations of MPA.