The thiol redox state of lymphoid organs is modified by immunization: Role of different immune cell populations
The thiol redox state of lymphoid organs is modified by immunization: Role of different immune cell populations
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DOI：
10.1002/eji.200838439
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发表时间：
2008-09-01
影响因子：
5.4
通讯作者：
Rubartelli, Anna
中科院分区：
文献类型：
--
作者：
Castellani, Patrizia;Angelini, Giovanna;Rubartelli, Anna
静息T淋巴细胞可以内化还原半胱氨酸（Cys），但不能内化胱氨酸，胱氨酸是细胞外占主导地位的氨基酸的氧化形式。体外研究表明，DC在抗原呈递过程中向T细胞提供Cys，使其活化。在这里，我们表明，增加硫醇生产是体内免疫反应的标志。事实上，LN的巯基含量在抗原注射后显著增加。非蛋白质巯基与DC共分布，并且在生发中心中高度丰富。与此一致，活化但非静息B淋巴细胞和巨噬细胞释放游离巯基。活化后增加的巯基释放需要硫氧还蛋白，并通过增加的硫氧还蛋白表达来抑制。LN的T区始终较少染色，并且静息和活化的T细胞都不能释放硫醇。有趣的是，胱氨酸/谷氨酸转运蛋白x（c）-在静息T淋巴细胞中不存在，但在体外被TCR触发快速诱导，表明T细胞从外源性Cys的需要中释放在活化后早期发生。这些结果表明，还原性微环境对于启动免疫应答是必不可少的，但不利于其进化，并支持细胞外氧化还原参与控制关键细胞功能的新兴概念。
Resting T lymphocytes can internalize reduced cysteine (Cys) but not cystine, the oxidized form of the amino acid that predominates extracellularly. In vitro studies have shown that DC provide Cys to T cells during antigen presentation, allowing their activation. Here, we show that increased thiol production is a hallmark of immune response in vivo. Indeed, the thiol content of LN increases dramatically after antigen injection. Non-protein thiols co-distribute with DC and are highly abundant in germinal centers. In agreement, activated but not resting B lymphocytes and macrophages release free thiols. Increased thiol release following activation requires thioredoxin and is paralleled by increased thioredoxin expression. The T zones of LN are consistently less stained, and both resting and activated T cells are unable to release thiols. Interestingly, the cystine/glutamate transporter x(c)- is absent in resting T lymphocytes but is rapidly induced by TCR triggering in vitro, indicating that the release of T cells from the need of exogenous Cys occurs early after activation. These results indicate that a reducing microenvironment is essential to start the immune response but dispensable for its evolution, and support the emerging concept that extracellular redox is implicated in the control of crucial cellular functions.