Protecting and rescuing the effectors: roles of differentiation and survival in the control of memory T cell development.
Protecting and rescuing the effectors: roles of differentiation and survival in the control of memory T cell development.
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DOI：
10.3389/fimmu.2012.00404
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发表时间：
2012
影响因子：
7.3
通讯作者：
Hildeman DA
中科院分区：
文献类型：
--
作者：
Kurtulus S;Tripathi P;Hildeman DA
疫苗可以说是改善人类健康的最重要的干预措施，它利用了免疫记忆现象。记忆T细胞的激发通常是成功的长寿保护性免疫的重要组成部分。TCR Tg小鼠和MHC四聚体染色试剂的开发极大地帮助了我们对T细胞记忆的理解，这些试剂允许精确跟踪抗原特异性T细胞应答。事实上，在急性感染或免疫后，幼稚T细胞经历了大规模的扩增，最终产生了强大的效应T细胞群。这种峰值效应反应相对短暂，虽然大多数效应T细胞因凋亡而死亡，但有些仍然存在并发育成记忆细胞。虽然这种细胞命运决定的分子机制仍然不完全确定，但已经取得了实质性进展，特别是关于CD 8 + T细胞。例如，在应答期间产生的效应CD 8 + T细胞是异质的，由具有或多或少发育成成熟记忆细胞的潜力的细胞组成。CD 8 + T细胞记忆的发展受到控制效应T细胞分化和存活的转录程序的调节。虽然抗原刺激的类型和炎症水平控制效应CD 8 + T细胞分化，但细胞因子的可用性及其控制Bcl-2家族成员表达和功能的能力决定了它们的存活。这些不同的分化和存活程序可以允许更精细的治疗干预来控制CD 8 + T细胞记忆的质量和数量。CD 4 + T细胞向记忆转变的效应子的特征不如CD 8 + T细胞，将讨论新出现的细节。本文将重点介绍近年来在T细胞记忆发展机制方面取得的进展，重点是效应T细胞存活的控制因素。
Vaccines, arguably the single most important intervention in improving human health, have exploited the phenomenon of immunological memory. The elicitation of memory T cells is often an essential part of successful long-lived protective immunity. Our understanding of T cell memory has been greatly aided by the development of TCR Tg mice and MHC tetrameric staining reagents that have allowed the precise tracking of antigen-specific T cell responses. Indeed, following acute infection or immunization, naïve T cells undergo a massive expansion culminating in the generation of a robust effector T cell population. This peak effector response is relatively short-lived and, while most effector T cells die by apoptosis, some remain and develop into memory cells. Although the molecular mechanisms underlying this cell fate decision remain incompletely defined, substantial progress has been made, particularly with regards to CD8+ T cells. For example, the effector CD8+ T cells generated during a response are heterogeneous, consisting of cells with more or less potential to develop into full-fledged memory cells. Development of CD8+ T cell memory is regulated by the transcriptional programs that control the differentiation and survival of effector T cells. While the type of antigenic stimulation and level of inflammation control effector CD8+ T cell differentiation, availability of cytokines and their ability to control expression and function of Bcl-2 family members governs their survival. These distinct differentiation and survival programs may allow for finer therapeutic intervention to control both the quality and quantity of CD8+ T cell memory. Effector to memory transition of CD4+ T cells is less well characterized than CD8+ T cells, emerging details will be discussed. This review will focus on the recent progress made in our understanding of the mechanisms underlying the development of T cell memory with an emphasis on factors controlling survival of effector T cells.