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揭示辅助 CD8+ T 细胞反应的机制。

Unravelling the mechanisms of help for CD8+ T cell responses.

机构信息

David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Rochester, NY, USA.

出版信息

Immunol Res. 2009 Dec;45(2-3):209-17. doi: 10.1007/s12026-009-8102-0. Epub 2009 Feb 18.

DOI:10.1007/s12026-009-8102-0
PMID:19224140
Abstract

CD8+ T cells are critically important for immune defense against many viral and bacterial pathogens, and are also key components of cancer immunotherapy. Help from CD4+ T cells is usually essential for optimal CD8+ T cell responses, driving the primary response, the survival of memory cells, and the generation of protective and therapeutic immunity. Understanding the mechanisms of help is thus essential for vaccine design, and for restoring protective immunity in immunosuppressed individuals. Our laboratory has developed an immunization protocol using peptide-pulsed dendritic cells to stimulate help-dependent primary, memory, and secondary CD8+ T cell responses. We have used gene-targeted and T cell receptor transgenic mice to identify two distinct pathways that generate help-dependent and help-independent CD8+ T cell responses, respectively, and are now starting to define the molecular mechanisms underlying these two pathways.

摘要

CD8+ T 细胞对于抵抗许多病毒和细菌病原体的免疫防御至关重要,也是癌症免疫疗法的关键组成部分。CD4+ T 细胞的帮助通常对于最佳 CD8+ T 细胞反应至关重要,它可以驱动初始反应、记忆细胞的存活以及保护性和治疗性免疫的产生。因此,了解辅助的机制对于疫苗设计以及恢复免疫抑制个体的保护性免疫至关重要。我们的实验室开发了一种使用肽脉冲树突状细胞刺激辅助依赖性原发性、记忆性和继发性 CD8+ T 细胞反应的免疫方案。我们已经使用基因靶向和 T 细胞受体转基因小鼠来分别鉴定出产生辅助依赖性和辅助非依赖性 CD8+ T 细胞反应的两条不同途径,现在我们开始定义这两条途径的分子机制。

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Unravelling the mechanisms of help for CD8+ T cell responses.揭示辅助 CD8+ T 细胞反应的机制。
Immunol Res. 2009 Dec;45(2-3):209-17. doi: 10.1007/s12026-009-8102-0. Epub 2009 Feb 18.
2
Nonspecific CD4(+) T cells with uptake of antigen-specific dendritic cell-released exosomes stimulate antigen-specific CD8(+) CTL responses and long-term T cell memory.摄取抗原特异性树突状细胞释放的外泌体的非特异性CD4(+) T细胞刺激抗原特异性CD8(+) CTL反应和长期T细胞记忆。
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Direct CD4 help provision following interaction of memory CD4 and CD8 T cells with distinct antigen-presenting dendritic cells.直接提供 CD4 帮助,以在记忆性 CD4 和 CD8 T 细胞与不同的抗原呈递树突状细胞相互作用后。
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本文引用的文献

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Cutting edge: CD4+ T cell-derived IL-2 is essential for help-dependent primary CD8+ T cell responses.前沿:CD4+ T细胞衍生的白细胞介素-2对于依赖辅助的初始CD8+ T细胞反应至关重要。
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Shaping and reshaping CD8+ T-cell memory.塑造和重塑CD8+T细胞记忆。
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Effector CD8 T cell development: a balancing act between memory cell potential and terminal differentiation.效应性CD8 T细胞的发育:记忆细胞潜能与终末分化之间的平衡行为。
Basal gene expression by lung CD4+ T cells in chronic obstructive pulmonary disease identifies independent molecular correlates of airflow obstruction and emphysema extent.
慢性阻塞性肺疾病中肺CD4+ T细胞的基础基因表达可确定气流阻塞和肺气肿程度的独立分子关联。
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Critical role for IL-21 in both primary and memory anti-viral CD8+ T-cell responses.IL-21 在原发性和记忆性抗病毒 CD8+ T 细胞反应中均具有重要作用。
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Translating insights from persistent LCMV infection into anti-HIV immunity.将持续 LCMV 感染的研究进展转化为抗 HIV 免疫。
Immunol Res. 2010 Dec;48(1-3):3-13. doi: 10.1007/s12026-010-8162-1.
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Bridging innate and adaptive antitumor immunity targeting glycans.靶向聚糖桥接固有免疫和适应性抗肿瘤免疫
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The potential of CD4 T-cell memory.CD4 T 细胞记忆的潜力。
Immunology. 2010 May;130(1):1-9. doi: 10.1111/j.1365-2567.2010.03259.x. Epub 2010 Mar 16.
9
Dynamic regulation of functionally distinct virus-specific T cells.功能不同的病毒特异性 T 细胞的动态调节。
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10
Immunology at the university of Rochester.罗切斯特大学的免疫学。
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Differential role of IL-2R signaling for CD8+ T cell responses in acute and chronic viral infections.白细胞介素-2受体信号在急性和慢性病毒感染中对CD8 + T细胞反应的不同作用。
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Chemokine-guided CD4+ T cell help enhances generation of IL-6RalphahighIL-7Ralpha high prememory CD8+ T cells.趋化因子引导的CD4 + T细胞辅助增强了IL-6Rα高IL-7Rα高的前记忆CD8 + T细胞的生成。
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Efficient T cell activation via a Toll-Interleukin 1 Receptor-independent pathway.通过Toll样白细胞介素1受体非依赖性途径实现高效T细胞活化。
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Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells.启动过程中的白细胞介素-2信号是CD8 +记忆T细胞二次扩增所必需的。
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Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction.趋化因子通过引导初始CD8 + T细胞至CD4 + T细胞与树突状细胞相互作用的部位来增强免疫力。
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Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection.I型干扰素直接作用于CD8 T细胞,以使其在病毒感染时发生克隆扩增并形成记忆细胞。
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Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination.树突状细胞疫苗接种后加速的CD8 + T细胞记忆及初免-加强反应
Nat Med. 2005 Jul;11(7):748-56. doi: 10.1038/nm1257. Epub 2005 Jun 12.