Azodicarbonamide as a new T cell immunosuppressant: Synergy with cyclosporin A

We recently demonstrated that azodicarbonamide is an immunosuppressive comp ound that inhibits calcium mobilization in T lymphocytes. In this study, we show that azodicarbonamide prevents the progression of human CD4(+) T lymp hocytes into the G1 phase of the cell cycle, inhibits their blastogenesis, down-regulates their membrane expression of CD25 and CD69, and decreases th eir transcription of cytokine genes. Addition of the calcium ionophore A231 87 completely restores T cell proliferation in the presence of azodicarbona mide. Furthermore, azodicarbonamide synergizes with cyclosporin A to inhibi t CD4+ T cell proliferation. In conclusion, the immunosuppressive action of azodicarbonamide is mainly related to its effect on the calcium mobilizati on machinery and is synergistic with that of calcineurin inhibitors. (C) 20 01 Academic Press.