免疫抑制剂增强T细胞凋亡

Augmentation of T-cell apoptosis by immunosuppressive agents.

作者信息

Takahashi K, Reynolds M, Ogawa N, Longo D L, Burdick J

机构信息

The Johns Hopkins Medical Institutions, Baltimore, MD, USA.

出版信息

Clin Transplant. 2004;18 Suppl 12:72-5. doi: 10.1111/j.1399-0012.2004.00222.x.

DOI:10.1111/j.1399-0012.2004.00222.x

PMID:15217412

Abstract

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.

摘要

T细胞中凋亡（活化诱导的细胞死亡，AICD）的调节益处可能会受到免疫抑制剂的影响。我们将霉酚酸酯（MMF，使用其活性代谢产物霉酚酸（MPA））与雷帕霉素（RAPA）以及钙调神经磷酸酶抑制剂（CI）环孢素（CYA）和他克莫司（FK）进行了比较研究。来自外周血白细胞（PBL）的纯T细胞用抗CD3加抗CD28进行刺激。通过羧基荧光素二乙酸琥珀酰亚胺酯（CFSE）的连续队列减少来测量细胞分裂，以在第4天有无添加药物的情况下测量增殖并确定不同细胞代的状态。使用流式细胞术通过膜联蛋白V染色对活化细胞进行凋亡检测。我们在这个严格的系统中证实了CI对AICD的抑制作用，并表明RAPA处于中间水平，而MPA在增强AICD方面最有效。