CD4(+)CD25(+) immune regulatory cells are required for induction of tolerance to alloantigen via costimulatory blockade.
CD4(+)CD25(+) immune regulatory cells are required for induction of tolerance to alloantigen via costimulatory blockade.
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DOI：
10.1084/jem.193.11.1311
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发表时间：
2001-06-04
期刊：
影响因子：
--
通讯作者：
Blazar BR
中科院分区：
文献类型：
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作者：
Taylor PA;Noelle RJ;Blazar BR
免疫调节 CD4+CD25+ 细胞在自我耐受的诱导和维持中发挥着至关重要的作用，对于 T 细胞稳态和预防自身免疫至关重要。诱导对同种异体供体移植物的耐受是骨髓和实体器官移植的临床理想目标。为了确定 CD4+CD25+ 细胞是否调节 T 细胞对同种异体抗原的反应并对诱导耐受至关重要，小鼠 CD4+ T 细胞通过离体 CD40 配体 (CD40L)/CD40 或 CD28/细胞毒性 T 淋巴细胞相关抗原 4/B7 阻断来耐受同种异体抗原，导致继发性混合白细胞反应低反应性和体内对同种异体抗原的耐受性。 CD4+CD25+T细胞被发现是同种异体反应的有效调节剂。 CD4+应答者群体中CD4+CD25+T细胞的耗竭完全消除了对同种异体抗原的离体耐受诱导，如通过体外和体内对同种异体抗原再刺激的完整反应所测量的。将 CD4+CD25+ T 细胞回加到 CD4+CD25− 培养物中可恢复耐受诱导。这些数据首次表明 CD4+CD25+ 细胞对于诱导同种异体抗原耐受至关重要，并且对于针对 T 细胞共刺激途径的耐受诱导策略具有重要意义。
Immune regulatory CD4+CD25+ cells play a vital role in the induction and maintenance of self-tolerance and are essential for T cell homeostasis and the prevention of autoimmunity. Induction of tolerance to allogeneic donor grafts is a clinically desirable goal in bone marrow and solid organ transplantation. To determine whether CD4+CD25+ cells regulate T cell responses to alloantigen and are critical for tolerance induction, murine CD4+ T cells were tolerized to alloantigen via ex vivo CD40 ligand (CD40L)/CD40 or CD28/cytotoxic T lymphocyte–associated antigen 4/B7 blockade resulting in secondary mixed leukocyte reaction hyporesponsiveness and tolerance to alloantigen in vivo. CD4+CD25+ T cells were found to be potent regulators of alloresponses. Depletion of CD4+CD25+ T cells from the CD4+ responder population completely abrogated ex vivo tolerance induction to alloantigen as measured by intact responses to alloantigen restimulation in vitro and in vivo. Addback of CD4+CD25+ T cells to CD4+CD25− cultures restored tolerance induction. These data are the first to indicate that CD4+CD25+ cells are essential for the induction of tolerance to alloantigen and have important implications for tolerance-inducing strategies targeted at T cell costimulatory pathways.