嘌呤生成性免疫缺陷疾病：脱氧核糖核苷对T细胞的选择性毒性。
Purinogenic immunodeficiency diseases: selective toxicity of deoxyribonucleosides for T cells.
作者信息
Mitchell B S, Mejias E, Daddona P E, Kelley W N
出版信息
Proc Natl Acad Sci U S A. 1978 Oct;75(10):5011-4. doi: 10.1073/pnas.75.10.5011.
Abstract
Deoxyadenosine at low concentrations and in the presence of an inhibitor of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) is markedly toxic to lymphoblast cell lines of T cell origin but does not impair growth of B cell lines. Deoxyguanosine is also more toxic for T lymphoblasts. In the presence of deoxyadenosine or deoxyguanosine, elevation of the corresponding deoxyribonucleoside triphosphate (dATP or dGTP) occurs in T cell, but not in B cell, lines. The addition of deoxycytidine or dipyridamole results in lower dATP and dGTP levels and prevents deoxyribonucleoside toxicity. These findings provide a molecular basis for the immunodeficiency observed in individuals with several inborn errors of purine metabolism.
摘要
低浓度的脱氧腺苷在腺苷脱氨酶（腺苷氨基水解酶，EC 3.5.4.4）抑制剂存在的情况下，对T细胞来源的淋巴母细胞系具有显著毒性，但不影响B细胞系的生长。脱氧鸟苷对T淋巴母细胞也更具毒性。在脱氧腺苷或脱氧鸟苷存在的情况下，T细胞系中相应的脱氧核糖核苷三磷酸（dATP或dGTP）水平会升高，但B细胞系中不会。添加脱氧胞苷或双嘧达莫会导致dATP和dGTP水平降低，并防止脱氧核糖核苷毒性。这些发现为患有几种嘌呤代谢先天性缺陷的个体中观察到的免疫缺陷提供了分子基础。
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