CXCL12 Induction of Inducible Nitric Oxide Synthase in Human CD8 T Cells
CXCL12 Induction of Inducible Nitric Oxide Synthase in Human CD8 T Cells
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DOI：
10.1016/j.healun.2008.08.014
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发表时间：
2008-12-01
影响因子：
8.9
通讯作者：
Pober, Jordan S.
中科院分区：
文献类型：
--
作者：
Choy, Jonathan C.;Yi, Tai;Pober, Jordan S.
背景资料：我们以前报道，诱导型一氧化氮合酶（iNOS）的表达在移植物浸润的人T细胞，这是局限于旁观者的人口有助于T细胞介导的排斥反应的同种异体移植动脉在人源化小鼠模型。在此，我们研究是否CXCL 12，一种被认为有助于募集旁观者T细胞的趋化因子，诱导人CD 8 T细胞中的iNOS。此外，人同种异体移植动脉的iNOS和CD 8，和相邻的切片染色CXCL 12，以确定其在人体tissues.Results的定位：休息的人CD 8和CD 4 T细胞表达CXCR 4，但不CXCR 7，受体CXCL 12。CXCL 12处理诱导表达iNOS mRNA和蛋白在原代人CD 8 T细胞中以剂量依赖性方式，但对CD 4 T细胞没有影响。诱导CD 8 T细胞中的iNOS表达通过增加基因转录介导。T细胞受体（TCR）活化的CD 8 T细胞迅速下调CXCR 4，这与CXCL 12在活化的T细胞中诱导iNOS的能力减弱一致。在人源化小鼠同种异体移植物动脉排斥模型和冠状动脉临床标本中，浸润的人CD 8 T细胞中iNOS的表达与CXCL 12的表达在空间上相关。结论：CXCL 12诱导人CD 8 T细胞中iNOS的表达，这种反应可能有助于同种异体移植物排斥。J Heart Lung Transplant 2008;27：1333-9.版权所有（C）2008国际心肺移植学会。
Background: We reported previously that inducible nitric oxide synthase (iNOS) expression in graft-infiltrating human T cells that is confined to the bystander population contributes to T-cell-mediated rejection of allograft arteries in a humanized mouse model. Herein we examine whether CXCL12, a chemokine thought to contribute to recruitment of bystander T cells, induces iNOS in human CD8 T cells.Methods: Human CD8 T cells were treated with CXCL12 and iNOS expression was examined. Also, human allograft arteries were immunohistochemically stained for iNOS and CD8, and adjacent sections stained for CXCL12 to determine their localization in human tissues.Results: Resting human CD8 and CD4 T cells expressed the CXCR4, but not the CXCR7, receptor for CXCL12. Treatment with CXCL12 induced expression of both iNOS mRNA and protein in primary human CD8 T cells in a dose-dependent manner, but had no effect on CD4 T cells. Induction of iNOS expression in CD8 T cells was mediated by increased gene transcription. T-cell-receptor (TCR)-activated CD8 T cells rapidly downregulated CXCR4, which coincided with diminished ability of CXCL12 to induce iNOS in activated T cells. iNOS expression in infiltrating human CD8 T cells was spatially associated with CXCL12 expression both in the humanized mouse model of allograft artery rejection and in clinical specimens of coronary arteries displaying allograft vasculopathy.Conclusions: CXCL12 induces iNOS expression in human CD8 T cells and this response may contribute to allograft rejection. J Heart Lung Transplant 2008;27:1333-9. Copyright (C) 2008 by the International Society for Heart and Lung Transplantation.