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Abstract

Aim Belatacept (BLT) has recently been approved in renal transplantation so as to avoid side effects of CNI. However, the effect of BLT alone or in combination with other maintenance agents on regulatory T cells is not clear. Methods We tested BLT and Mycophenolic Acid (MPA; active form of Cellcept or Myfortic being used clinically together with BLT), either singly or in combinations in vitro in healthy volunteers using (a) 3 H-TdR incorporation to measure inhibition of lymphoproliferation, and (b) flow cytometry to estimate newly generated CD4 + CD25 High FOXP3 + Tregs in CFSE labeled MLR responders. Results In comparison to medium controls, BLT dose-dependently inhibited both proliferation and Treg generation in MLRs (n = 9). MPA, when tested singly in MLR, inhibited lymphoproliferation but enhanced Treg generation at sub-therapeutic (p Table 1 ]. However, purified CD4 + CD127 − cells generated in MLR in presence of 1 or 10 μ g/ml MPA and then tested as third component modulators in fresh MLR, significantly enhanced newly developed Tregs in the proliferating responder cells, vs. BLT or medium controls (n = 3). Conclusions BLT and MPA had opposite effects on Treg generation in MLR. Combinations of the two may have positive overall Treg generating effects. Mathew: Bristol-Myers-Squibb: Grant Research. Miller: Bristol-Myers-Squibb: Grant Research. Levitsky: Bristol-Myers-Squibb: Grant Research.