Augmentation of T-cell apoptosis by immunosuppressive agents.

The regulatory benefit of apoptosis (activation-induced cell death, AICD) in T cells can be influenced by immunosuppressive agents. We examined this for mycophenolate mofetile (MMF, using it's active metabolite, mycophenolate (MPA)) compared with rapamycin (RAPA) and the calcineurin inhibitors (CI) cyclosporin (CYA) and FK506 (FK). Pure T cells from peripheral blood leucocytes (PBL) were stimulated by anti-CD3 plus anti-CD28. Cell division (sequential cohort reduction in carboxyflourescein diacetate succinimidyl ester, CFSE) was used to measure proliferation and determine status of different cell generations without or with added drug at 4 d. Apoptosis was measured by Annexin V staining of activated cells using flow cytometry. We confirmed in this stringent system the inhibition of AICD by CI and showed that RAPA is intermediate and MPA most effective in this potentiation of AICD.