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对三种对脱氧腺苷加脱氧助间型霉素具有不同敏感性的T淋巴细胞系的特性分析。

Characterization of three T-lymphoid cell lines with distinct sensitivities to deoxyadenosine plus deoxycoformycin.

作者信息

Duan D S, Smith W, Sadée W, Cowan M J

机构信息

Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco 94143.

出版信息

Thymus. 1992 Feb;19(1):1-11.

PMID:1373528
Abstract

Three established human T-cell lines, HPB-MLT, HPB-ALL and PEER, were characterized and tested for their sensitivity to deoxyadenosine (dAdo) plus deoxycoformycin (dCoF). Phenotypic characterizations showed that all three cell lines had receptors for peanut agglutinin (PNA) and soybean agglutinin (SBA) while HPB-MLT and HPB-ALL, but not PEER, expressed the cortical thymocyte-specific marker, CD1. The majority of HPB-MLT cells (88%) expressed only CD4 but not CD8 antigen while most HPB-ALL cells (81%) co-expressed CD8 and CD4 antigens. PEER cells were negative for both CD8 and CD4. These three T cell lines showed differential sensitivity to dAdo plus dCoF in consequent tests. dAdo or dAdo plus dCoF (1 microM) had no effect on the growth, or DNA and RNA synthesis of HPB-MLT cells while the combination of dAdo and dCoF partially inhibited cellular growth and DNA and RNA synthesis of HPB-ALL cells. Further, the growth and DNA and RNA synthesis of PEER cells were strongly inhibited by the combination of dAdo and dCoF. This high sensitivity to dAdo plus dCoF reflected an immature phenotype of PEER cells despite its expression of CD3. Flow cytometric analysis of PEER cells demonstrated disappearance of the G2/M phase cells from the cell cycle after treatment with dAdo plus dCoF. Measurements of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities in all three cell lines, however, did not establish correlations between purine metabolizing enzyme activities and the differential sensitivities to dAdo plus dCoF. In sum, we report here three T-cell lines of different phenotypes that displayed significantly different sensitivities to dAdo plus dCoF which may facilitate investigations on the mechanisms of ADA deficiency.

摘要

对三种已建立的人T细胞系HPB-MLT、HPB-ALL和PEER进行了特性鉴定,并检测了它们对脱氧腺苷(dAdo)加脱氧助间霉素(dCoF)的敏感性。表型特征表明,这三种细胞系都有花生凝集素(PNA)和大豆凝集素(SBA)的受体,而HPB-MLT和HPB-ALL表达皮质胸腺细胞特异性标志物CD1,PEER则不表达。大多数HPB-MLT细胞(88%)仅表达CD4抗原而不表达CD8抗原,而大多数HPB-ALL细胞(81%)同时表达CD8和CD4抗原。PEER细胞的CD8和CD4均为阴性。在随后的试验中,这三种T细胞系对dAdo加dCoF表现出不同的敏感性。dAdo或dAdo加dCoF(1 microM)对HPB-MLT细胞的生长、DNA和RNA合成没有影响,而dAdo和dCoF的组合则部分抑制了HPB-ALL细胞的生长以及DNA和RNA合成。此外,dAdo和dCoF的组合强烈抑制了PEER细胞的生长以及DNA和RNA合成。尽管PEER细胞表达CD3,但它对dAdo加dCoF的这种高敏感性反映了其不成熟的表型。对PEER细胞进行流式细胞术分析表明,用dAdo加dCoF处理后,细胞周期中的G2/M期细胞消失。然而,对所有三种细胞系中腺苷脱氨酶(ADA)和嘌呤核苷磷酸化酶(PNP)活性的测量并未建立嘌呤代谢酶活性与对dAdo加dCoF的不同敏感性之间的相关性。总之,我们在此报告了三种不同表型的T细胞系,它们对dAdo加dCoF表现出显著不同的敏感性,这可能有助于对ADA缺乏机制的研究。

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