In-vitro effects of cyclosporin A, FK506, 6-mercaptopurine, and prednisolone on lymphokine-activated killer cells.
In-vitro effects of cyclosporin A, FK506, 6-mercaptopurine, and prednisolone on lymphokine-activated killer cells.
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环孢素 A、FK506、6-巯基嘌呤和泼尼松龙对淋巴因子激活的杀伤细胞的体外作用。
DOI：
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发表时间：
1994
影响因子：
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通讯作者：
F. Berthoux
中科院分区：
文献类型：
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作者：
E. Alamartine;O. Sabido;F. Berthoux
在移植受者中，免疫抑制方案对自然杀伤（NK）细胞和淋巴因子激活的杀伤（LAK）细胞是有害的，这些细胞除了其众所周知的抗肿瘤活性外还显示出许多重要的生物学功能。为了发现哪种方案可以保留NK和LAK功能，我们测试了CsA、FK 506、6-巯基嘌呤和泼尼松龙在体外IL-2活化过程中对HLA非限制性细胞毒性的影响。对于每种药物，我们从11名健康志愿者获得外周血样品。将非粘附PBMC与浓度范围为0至10微克/毫升的CsA、FK 506、6-巯基嘌呤或泼尼松龙一起孵育2天，以筛选治疗剂量以下、治疗剂量和治疗剂量以上的剂量。此后，加入100 IU的IL-2，再培养3天。培养前后分别用抗CD_3/CD_（16）/CD_（56）抗体直接免疫荧光染色法检测细胞亚群;用细胞裂解法检测LAK活性;环孢菌素和FK 506对LAK细胞毒活性和LAK细胞数无明显影响，而泼尼松龙和6-巯基嘌呤均能降低LAK细胞毒活性、CD 3-CD 16 + CD 56+细胞数和胸苷摄取。LAK细胞的杀伤活性与CD 3-CD 16 + CD 56+细胞数相关，而与CD 3 + CD 16-CD 56-细胞数无关，且随着TdR掺入量的增加，LAK细胞的杀伤活性增强。后者与CD 3-CD 16 + CD 56+细胞的数量相关，但与CD 3 + CD 16-CD 56-细胞的数量无关。（250字处删节）
In transplant recipients, immunosuppressive regimens are deleterious on natural killer (NK) and lymphokine-activated killer (LAK) cells, which beyond their well-known antitumoral activity display many important biological functions. In order to find which regimens could preserve NK and LAK functions we tested the influence of CsA, FK506, 6-mercaptopurine and prednisolone on HLA-unrestricted cytotoxicity during an in-vitro IL-2 activation. For each drug we obtained peripheral blood samples from 11 healthy volunteers. Non-adherent PBMC were incubated 2 days with either CsA, FK506, 6-mercaptopurine or prednisolone, whose concentrations ranged from 0 to 10 micrograms/ml, in order to screen infratherapeutic, therapeutic, and supratherapeutic doses. Thereafter, 100 IU of IL-2 were added for a further 3-day culture. Before and after the culture, we analysed (1) the cell subsets by direct immunofluorescence staining with anti-CD3/CD16/CD56 antibodies, (2) the LAK activity with the lysis of Daudi cells, (3) the cell proliferation with a 24-h incorporation of thymidine. Cyclosporin and FK506 did not impair the LAK cytotoxicity nor the number of LAK cells, whereas both prednisolone and 6-mercaptopurine decreased the LAK cytotoxicity, the number of CD3- CD16+ CD56+ cells, and the thymidine uptake. As a whole, the LAK cytotoxicity was correlated with the number of CD3- CD16+ CD56+ cells but not with the number of CD3+ CD16- CD56- cells, and it also increased with the incorporation of thymidine. This latter was correlated with the number of CD3- CD16+ CD56+ cells, but not with the number of CD3+ CD16- CD56- cells.(ABSTRACT TRUNCATED AT 250 WORDS)