CD8+ T cell exhaustion during persistent viral infection is regulated independently of the virus-specific T cell receptor.
CD8+ T cell exhaustion during persistent viral infection is regulated independently of the virus-specific T cell receptor.
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DOI：
10.3109/08820139.2012.751397
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发表时间：
2013
影响因子：
2.8
通讯作者：
Teague RM
中科院分区：
文献类型：
--
作者：
Jackson SR;Berrien-Elliott MM;Meyer JM;Wherry EJ;Teague RM
在慢性病毒感染期间，病毒特异性CD8+T细胞的反应由于获得功能缺陷和细胞数量减少而被边缘化，这一过程被定义为T细胞耗尽。T细胞对自身抗原的耐受性还表现为效应器功能受损和自身反应性T细胞的最终缺失。诱导耐受和衰竭涉及许多共同的抑制机制，因此类似的治疗方法在这些不同的环境中被证明是有效的。我们以前曾证明，表达双T细胞受体的耐受性自身反应性CD8+T细胞(即双T细胞受体)可以通过第二个针对外来抗原的TCR而被拯救。这些数据表明，T细胞的耐受性是在自身反应性TCR的水平上调节的。在这里，双TCR CD8+T细胞被用来检查持续病毒感染期间的疲惫是否可以通过第二个不参与识别病毒的TCR来通过类似的免疫策略来挽救。与耐受性CD8+T细胞可实现的挽救直接相反，耗尽的T细胞在两种TCR中受到同等程度的损害。这些发现表明，耗竭是由病毒特异性TCR下游的缺陷维持的，并确立了耗竭和耐受是T细胞功能障碍的明显调节状态。
During chronic viral infections, responses by virus-specific CD8+ T cells become marginalized by the acquisition of functional defects and reduced cell numbers in a process defined as T cell exhaustion. T cell tolerance to self-antigen is also characterized by impaired effector function and eventual deletion of self-reactive T cells. Induction of both tolerance and exhaustion involve many shared inhibitory mechanisms, thus similar therapeutic approaches have proven effective in these distinct environments. We previously demonstrated that tolerant self-reactive CD8+ T cells expressing dual-T cell receptors (i.e. dual-TCR) could be rescued by immunization through a second TCR specific for a foreign antigen. These data revealed that T cell tolerance was regulated at the level of the self-reactive TCR. Here, dual-TCR CD8+ T cells were used to examine if exhaustion during persistent viral infection could be rescued by an analogous strategy of immunization through a second TCR not involved in recognition of virus. In direct contrast to the rescue achievable in tolerant CD8+ T cells, exhausted T cells were equally impaired through both TCR. These findings suggest that exhaustion is maintained by defects downstream of the virus-specific TCR, and establish that exhaustion and tolerance are distinctly regulated states of T cell dysfunction.
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募集高危险性CD8（+）T细胞的潜在池募集到抗肿瘤免疫反应中。
DOI：
10.1084/jem.20042167
发表时间：
2005-05-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ercolini AM;Ladle BH;Manning EA;Pfannenstiel LW;Armstrong TD;Machiels JP;Bieler JG;Emens LA;Reilly RT;Jaffee EM
通讯作者：
Jaffee EM
影响因子：
7
作者：
Kim PS;Ahmed R
通讯作者：
Ahmed R
影响因子：
5.4
作者：
Mueller, Katja;Schweier, Oliver;Pircher, Hanspeter
通讯作者：
Pircher, Hanspeter
影响因子：
20.3
作者：
Lucas, Carrie L.;Workman, Creg J.;Sykes, Megan
通讯作者：
Sykes, Megan
影响因子：
20.3
作者：
Bollard, CM;Rössig, C;Rooney, CM
通讯作者：
Rooney, CM