Folate deficiency inhibits the proliferation of primary human CD8+ T lymphocytes in vitro
Folate deficiency inhibits the proliferation of primary human CD8+ T lymphocytes in vitro
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DOI：
10.4049/jimmunol.173.5.3186
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Ames, BN
中科院分区：
文献类型：
--
作者：
Courtemanche, C;Elson-Schwab, I;Ames, BN
叶酸是一碳转移反应以及DNA和RNA合成所需的嘌呤和嘧啶的形成所必需的。叶酸缺乏可导致许多临床异常，包括大红细胞性贫血、心血管疾病、出生缺陷和致癌。由于叶酸缺乏引起的核苷酸失衡导致细胞周期停滞在S期和尿嘧啶错误掺入DNA中，这可能导致修复过程中DNA双链断裂。叶酸在免疫系统中的作用尚未完全确定。我们在不同浓度的叶酸中培养PHA激活的人T淋巴细胞，并测量增殖、细胞周期、凋亡、尿嘧啶错误掺入以及Th细胞（CD4（+））和细胞毒性T细胞（CD8（+））的比例。叶酸缺乏降低T淋巴细胞的增殖，诱导细胞周期停滞在S期，诱导细胞凋亡，并增加DNA中尿嘧啶的水平。叶酸缺乏也增加了CD4（+）与CD8（+）的比例，由于CD8（+）细胞增殖显着减少。叶酸或核苷补充叶酸缺乏细胞迅速恢复T淋巴细胞增殖和正常细胞周期，减少DNA尿嘧啶含量，降低CD4（+）与CD8（+）的比例。这些数据表明，叶酸状态可能会影响免疫系统，通过降低CD8（+）细胞的增殖能力，以响应激活。
Folate is required for one-carbon transfer reactions and the formation of purines and pyrimidines for DNA and RNA synthesis. Deficiency of folate can lead to many clinical abnormalities, including macrocytic anemia, cardiovascular diseases, birth defects, and carcinogenesis. The nucleotide imbalance due to folate deficiency causes cell cycle arrest in the S phase and uracil misincorporation into DNA, which may result in DNA double-strand breaks during repair. The role of folate in the immune system has not been fully characterized. We cultured PHA-activated human T lymphocytes in varying concentrations of folate, and measured proliferation, cell cycle, apoptosis, uracil misincorporation, and proportions of Th cells (CD4(+)) and cytotoxic T (CD8(+)) cells. Folate deficiency reduced proliferation of T lymphocytes, induced cell cycle arrest in the S phase, induced apoptosis, and increased the level of uracil in DNA. Folate deficiency also increased the CD4(+) to CD8(+) ratio due to a marked reduction of CD8(+) cell proliferation. Folate or nucleoside repletion of folate-deficient cells rapidly restored T lymphocyte proliferation and normal cell cycle, reduced the DNA uracil content, and lowered the CD4(+) to CD8(+) ratio. These data suggest that folate status may affect the immune system by reducing the capacity of CD8(+) cells to proliferate in response to activation.