Azodicarbonamide as a new T cell immunosuppressant: synergy with cyclosporin A.

We recently demonstrated that azodicarbonamide is an immunosuppressive compound that inhibits calcium mobilization in T lymphocytes. In this study, we show that azodicarbonamide prevents the progression of human CD4+ T lymphocytes into the G1 phase of the cell cycle, inhibits their blastogenesis, down-regulates their membrane expression of CD25 and CD69, and decreases their transcription of cytokine genes. Addition of the calcium ionophore A23187 completely restores T cell proliferation in the presence of azodicarbonamide. Furthermore, azodicarbonamide synergizes with cyclosporin A to inhibit CD4+ T cell proliferation. In conclusion, the immunosuppressive action of azodicarbonamide is mainly related to its effect on the calcium mobilization machinery and is synergistic with that of calcineurin inhibitors.