IL-12 reverses anergy to T cell receptor triggering in human lung tumor-associated memory T cells
IL-12 reverses anergy to T cell receptor triggering in human lung tumor-associated memory T cells
复制标题
DOI：
10.1016/j.clim.2005.09.008
复制
发表时间：
2006-02-01
影响因子：
8.6
通讯作者：
Bankert, RB
中科院分区：
文献类型：
--
作者：
Broderick, L;Brooks, SP;Bankert, RB
人类非小细胞肺癌中的记忆T细胞对肿瘤的进展没有反应。通过免疫荧光共聚焦显微镜成像核因子-kappaB和NFAT的核转位，在单细胞水平上评估T细胞，作为对T细胞受体触发的早期反应性的测量。在正常供者外周血T细胞发生最大移位的条件下，肿瘤相关T细胞在CD3+CD28交联剂作用下几乎不发生核因子-kappaB或NFAT的移位。肿瘤坏死因子-α在这些T细胞中诱导了最大的核因子-kappaB易位，表明它们仍能接受其他信号通路，在TCR触发之前用IL-12脉冲可以逆转它们的表观无能。来自其他慢性炎症微环境的T细胞对TCR激活表现出类似的难治性，这表明要么是微环境中存在的共同调节机制控制了这些细胞，要么是由于持续的抗原暴露，它们仍然难以通过TCR激活。(C)2005 Elsevier Inc.保留所有权利。
Memory T cells in human non-small cell lung cancer are unresponsive to progressing tumors. T cells were evaluated at the single cell level by imaging the nuclear translocation of NF-kappa B and NFAT via immunofluorescence confocal microscopy as an early measure of responsiveness to T cell receptor triggering. Little translocation of NF-kappa B or NFAT occurred in tumor-associated T cells in response to CD3+CD28 cross-linking under conditions which led to maximal translocation in normal donor peripheral blood T cells. TNF-alpha induced maximal NF-kappa B translocation in these T cells, indicating that they remain receptive to alternative signaling pathways, and pulsing with IL-12 prior to TCR triggering reversed their apparent anergy. T cells from additional chronic inflammatory microenvironments demonstrated a similar refractoriness to TCR activation, suggesting either that a common regulatory mechanism present within the microenvironment controls these cells or that with continuous antigen exposure, they remain refractory to activation via the TCR. (c) 2005 Elsevier Inc. All rights reserved.