Induction of apoptosis of peripheral activated T lymphocytes by immunosuppressants / 中华器官移植杂志

ABSTRACT

Objective To investigate the effects and mechanisms of immunosuppressants on in- duction of apoptosis of peripheral T lymphocytes.Methods T lymphocytes were derived from healthy donors and activated by super antigen SEB.The rest or activated T lymphocytes were incubated with immunosuppressants such as myophenolate mofetil (MMF),cyclosporine A (CsA),FK506,azathio- prine (Aza),sirolimus (SRL),prednisone (Pred),and daclizumab (Dac,anti-CD25mAb),alone or combined,for 3 days.The incidence of apoptosis was determined by the methods of confocal microsco- py,flow cytometer,DNA-ladder fragmentation electrophoresis,and reverse transcription-polymerase chain reaction (RT-PCR) gene amplification profiles.The quantitive assay of IL-2 and Fas in the cul- ture medium was also performed using the enzyme linked immunosorbent assay kit.Results Apoptosis in rest T lymphocytes was just induced by Pred among various immunosuppressants.MMF,Aza,and Pred promoted apoptosis in activated T lymphocytes (P＜0.05,P＜0.01),but it was blocked by CsA,FK506,SRL,and Dac (P＜0.01).After adding two or three kinds of immunosuppressants, the incidence of apoptosis in activated T lymphocytes was apparently lower than in control group (P＜0.01).The expression of Fas and IL-2 by activated T lymphocytes was inhibited by FK506 and CsA (P＜0.05).Conclusion MMF,Aza,and Pred may induce apoptosis of activated T lymphocytes via the signal pathway of Fas/Fasl.CsA and FK506 could inhibit the apoptosis of activated T lymphocytes by blocking the production of IL-2.Also,SRL and Dac can block the apoptosis of activated T lympho- cyte by interfering with the effect of IL-2 on T lymphocytes activation process.