DECREASED LEVELS OF TOTAL AND REDUCED GLUTATHIONE IN CD4(+) LYMPHOCYTES IN COMMON VARIABLE IMMUNODEFICIENCY ARE ASSOCIATED WITH ACTIVATION OF THE TUMOR-NECROSIS-FACTOR SYSTEM - POSSIBLE IMMUNOPATHOGENIC ROLE OF OXIDATIVE STRESS
DECREASED LEVELS OF TOTAL AND REDUCED GLUTATHIONE IN CD4(+) LYMPHOCYTES IN COMMON VARIABLE IMMUNODEFICIENCY ARE ASSOCIATED WITH ACTIVATION OF THE TUMOR-NECROSIS-FACTOR SYSTEM - POSSIBLE IMMUNOPATHOGENIC ROLE OF OXIDATIVE STRESS
复制标题
DOI：
10.1182/blood.v86.4.1383.bloodjournal8641383
复制
发表时间：
1995-08-15
期刊：
影响因子：
20.3
通讯作者：
FROLAND, SS
中科院分区：
文献类型：
--
作者：
AUKRUST, P;SVARDAL, AM;FROLAND, SS
我们之前已经证明慢性免疫激活和增强活性氧的产生在常见的可变免疫缺陷（CVI）。在本研究中，我们检测了谷胱甘肽的水平，谷胱甘肽是主要的细胞内硫醇，在20名CVI患者和16名健康对照者的血浆、单核细胞和淋巴细胞亚群中起重要的氧化和炎症应激保护作用。与健康对照相比，CVI患者的CD4（+）淋巴细胞的总谷胱甘肽和还原性谷胱甘肽水平均显著降低，还原性谷胱甘肽与总谷胱甘肽的比例也显著降低。CD4（+）淋巴细胞中谷胱甘肽水平的下降在CD45RA（+）亚群中最为明显。CVI患者血浆总谷胱甘肽水平也显著降低。相比之下，与献血者的单核细胞相比，来自CVI患者的单核细胞显示出总谷胱甘肽和还原性谷胱甘肽水平的增加。CVI患者血清肿瘤坏死因子α (TNF α)水平显著升高，TNF α浓度与CD4（+）淋巴细胞谷胱甘肽耗竭密切相关。此外，在体内持续免疫激活、外周血CD4（+）淋巴细胞数量减少和脾肿大的CVI患者亚组中发现总谷胱甘肽和还原性谷胱甘肽水平最低。最后，补充谷胱甘肽单乙基酯的细胞培养可显著提高CVI患者外周血单个核细胞的白细胞介素-2的产生。CVI中的这些谷胱甘肽异常表明氧化应激增加，特别是在CD4（+）淋巴细胞中，细胞内还原型谷胱甘肽的耗竭可能对CVI的CD4（+）淋巴细胞功能和免疫缺陷具有深远的影响。(C) 1995年由美国血液病学会出版。
We have previously shown chronic immune activation and enhanced generation of reactive oxygen species in common variable immunodeficiency (CVI). In the present study, we examined levels of glutathione, the dominant intracellular thiol, that play an important protective role against oxidative and inflammatory stress in plasma and in monocytes and lymphocyte subsets in 20 CVI patients and in 16 healthy controls. CD4(+) lymphocytes from CVI patients had significantly lower levels of both total and reduced glutathione as well as a lower ratio of reduced to total glutathione compared with healthy controls. This decrease in glutathione levels in CD4(+) lymphocytes was most pronounced in the CD45RA(+) subset. Plasma levels of total glutathione were also significantly decreased in CVI. In contrast, monocytes from CVI patients exhibited increased levels of both total and reduced glutathione compared with blood donor monocytes. CVI patients had significantly raised serum levels of tumor necrosis factor alpha (TNF alpha) and TNF alpha concentration was strongly associated with glutathione depletion in CD4(+) lymphocytes. Furthermore, the lowest levels of both total and reduced glutathione were found in a subgroup of CVI patients characterized by persistent immune activation in vivo, decreased numbers of CD4(+) lymphocytes in peripheral blood, and splenomegaly. Finally, supplementation of cell cultures with glutathione-monoethyl ester did significantly enhance interleukin-2 production from peripheral blood mononuclear cells in CVI patients. These glutathione abnormalities in CVI indicate increased oxidative stress, particularly in CD4(+) lymphocytes, and intracellular depletion of reduced glutathione of the demonstrated magnitude may have profound implications for CD4(+) lymphocyte function and the immunodeficiency in CVI. (C) 1995 by The American Society of Hematology.