The thiol redox state of lymphoid organs is modified by immunization: Role of different immune cell populations

被引:63
作者
Castellani, Patrizia [1 ]
Angelini, Giovanna [1 ]
Delfino, Laura [1 ]
Matucci, Andrea [2 ]
Rubartelli, Anna [1 ]
机构
[1] Natl Inst Canc Res, Cell Biol Unit, I-16132 Genoa, Italy
[2] Univ Verona, Immunol Sect, Dept Pathol, I-37100 Verona, Italy
关键词
lymphocytes; macrophages; non-protein thiols; redox; thioredoxin;
D O I
10.1002/eji.200838439
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2419 / 2425
页数:7
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