Impaired Ca/calcineurin pathway in in vivo anergized CD4 T cells.

Impaired Ca/calcineurin pathway in in vivo anergized CD4 T cells.
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体内激活的 CD4 T 细胞中 Ca/钙调神经磷酸酶途径受损。

DOI:
10.1093/intimm/12.6.817
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发表时间:
2000
影响因子:
4.4
通讯作者:
T. Nakayama
T. Nakayama
中科院分区:
医学3区
文献类型:
--
作者:
M. Kimura;M. Yamashita;M. Kubo;M. Iwashima;C. Shimizu;K. Tokoyoda;J. Chiba;M. Taniguchi;M. Katsumata;T. Nakayama

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克隆无反应性是外周血T细胞诱导自身免疫耐受的机制之一。在这项研究中,我们使用了充分记录的系统,在体内管理的超抗原,葡萄球菌肠毒素B(SE B),诱导小鼠外周血T细胞的低反应性(无反应性)的状态,以破译这一过程的细胞内生化基础。发现体外活化T细胞的TCR诱导的Ca应答受损,其中磷脂酶C-γ 1的磷酸化存在显著缺陷。用钙离子载体和新建立的表达活性形式的钙调磷酸酶的转基因小鼠系进行的实验表明,体内SEB诱导的无反应性是通过选择性损害TCR诱导的Ca/钙调磷酸酶途径的激活来建立和/或维持的。
Clonal anergy is one of the mechanisms that may account for self tolerance induced in T cells in the periphery. In this study we used the well-documented system of in vivo administration of a superantigen, staphylococcal enterotoxin B (SEB), to induce a state of hyporesponsiveness (anergy) in murine peripheral T cells to decipher the intracellular biochemical basis for this process. The TCR-induced Ca response of in vitro activated T cells was found to be impaired with significant defects in the phosphorylation of phospholipase C-gamma 1. Experiments with calcium ionophore and newly established transgenic mouse lines that express an active form of calcineurin suggested that in vivo SEB-induced anergy is established and/or maintained by a selective impairment in the TCR-induced activation of the Ca/calcineurin pathway.
DOI: 10.1126/science.7694363
发表时间: 1993-11-05
期刊: SCIENCE
影响因子: 56.9
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DOI: --
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