Effect of immunosuppressive agents on human T and B lymphoblasts.
Effect of immunosuppressive agents on human T and B lymphoblasts.
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免疫抑制剂对人 T 和 B 淋巴母细胞的影响。
DOI：
10.1016/0006-2952(83)90580-4
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发表时间：
1983
影响因子：
5.8
通讯作者：
Kelley,WN
中科院分区：
文献类型：
--
作者：
Kazmers,IS;Daddona,PE;Dalke,AP;Kelley,WN
我们研究了不同免疫抑制药物对人T(MOLT-4)和B(MGL-8)淋巴母细胞生长的影响。此外，我们还研究了这些药物的淋巴毒性作用是否可以归因于对腺苷脱氨酶(DDA)或嘌呤核苷磷酸化酶(PNP)的抑制。结果表明，1-β-d-阿拉伯呋喃胞嘧啶(Ara-C)、甲氨蝶呤和百菌清对T细胞的毒性是B细胞的4~7倍，而硫唑嘌呤、6-硫代鸟嘌呤、6-硫代嘌呤和5-氟尿嘧啶对T细胞和B细胞的毒性均较高。环磷酰胺和氧尿嘧啶仅在30 0μM以上时具有淋巴毒性，脱氧腺苷(50μM)、脱氧鸟苷(10μM)和脱氧辅酶A(10μM)单独与每种药物联合使用时均不能增强T细胞毒性。所有受试药物均未抑制T或B淋巴母细胞的ADA或PNP活性。除Ara-C外，在任何一种药物存在下，dATP和dGTP均未在T淋巴母细胞中蓄积。我们的结论是，本研究中使用的细胞培养系统有助于鉴定淋巴毒性和T细胞特异性免疫抑制剂。然而，所研究的药物似乎都不是ADA或PNP的抑制剂或竞争性底物。
We have studied the effects of various immunosuppressive drugs on the growth of human-derived T (MOLT-4) and B (MGL-8) lymphoblasts. In addition, we have examined whether the lymphotoxic effect of any of these drugs could be attributed to inhibition of either adenosine deaminase (DDA) or purine nucleoside phosphorylase (PNP). Results indicated that 1-β-d-arabinofuranosylcytosine (Ara-C), methotrexate and chlorambucil were four to seven times more toxic for T than for B cells, while azathioprine, 6-thioguanine, 6-mercaptopurine, and 5-fluorouracil were highly toxic for both T and B cells. Cyclophosphamide and oxisuran were lymphotoxic only at concentrations exceeding 300 μM. Deoxyadenosine (50 μM), deoxyguanosine (10 μM) and deoxycoformycin (10 μM) failed to enhance T cell toxicity when individually combined with each drug. None of the drugs tested inhibited T or B lymphoblast ADA or PNP activity. With the exception of Ara-C, neither dATP nor dGTP accumulated in T lymphoblasts incubated in the presence of any of the drugs. We conclude that the cell culture system used in this investigation is useful for identifying lymphotoxic and T cell-specific immunosuppressive agents. However, none of the drugs studied appeared to function as an inhibitor of, or a competitive substrate for, either ADA or PNP.