Early Decision: Effector and Effector Memory T Cell Differentiation in Chronic Infection.
Early Decision: Effector and Effector Memory T Cell Differentiation in Chronic Infection.
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DOI：
10.2174/1573395509666131126231209
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发表时间：
2013-08
影响因子：
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通讯作者：
Stephens R
中科院分区：
文献类型：
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作者：
Opata MM;Stephens R
由于效应记忆T细胞（Tem）是慢性寄生虫感染引起的主要群体，增加我们对其功能、存活和衍生的了解，因为表型和功能上不同于中央记忆和效应T细胞，这对于这些疾病的疫苗开发至关重要。然而，在某些感染中，记忆T细胞维持增加的效应子功能;这可能需要持续抗原的存在，这也可能导致T细胞耗竭。或者，在不存在抗原的情况下，仅保留记忆细胞数量的增加，而没有作为中央记忆的增强的功能。为了了解对抗原的需求以及长寿或保护的潜力，必须了解每种类型记忆的来源。对数据的全面审查确立了从免疫应答的第一个小时起记忆（Teff）前体和效应T细胞（Teff）的存在。这表明了一个新的范式Teff分化不同的命题，Teff只出现后Teff的收缩。已经显示几种信号在记忆T细胞的产生中是重要的，例如由每个T细胞克隆感知的抗原呈递（抗原受体、共刺激、细胞因子）的“信号1-3”的整合强度。考虑到这些整合在抗原呈递细胞上的信号已经显示出决定Teff和Teff表型和数量的结果，必须在非常早期的阶段做出这个决定。似乎效应T细胞的压倒性扩增和在早期时间点无法在表型上区分记忆T细胞掩盖了这个重要的决定点。这并不排除重复刺激或慢性炎症环境对这些早期阶段产生的群体的影响。最近的研究表明，Teff是来自早期Teff，我们认为，这包括Tem以及Tcm。因此，我们提出了一个从幼稚到记忆的分化途径的可测试模型，表明Tem不是完全分化的效应细胞，而是来源于Sallusto等人最初在1999年提出的中央记忆T细胞，但此后一直存在争议。
As effector memory T cells (Tem) are the predominant population elicited by chronic parasitic infections, increasing our knowledge of their function, survival and derivation, as phenotypically and functionally distinct from central memory and effector T cells will be critical to vaccine development for these diseases. In some infections, memory T cells maintain increased effector functions, however; this may require the presence of continued antigen, which can also lead to T cell exhaustion. Alternatively, in the absence of antigen, only the increase in the number of memory cells remains, without enhanced functionality as central memory. In order to understand the requirement for antigen and the potential for longevity or protection, the derivation of each type of memory must be understood. A thorough review of the data establishes the existence of both memory (Tmem) precursors and effector T cells (Teff) from the first hours of an immune response. This suggests a new paradigm of Tmem differentiation distinct from the proposition that Tmem only appear after the contraction of Teff. Several signals have been shown to be important in the generation of memory T cells, such as the integrated strength of “signals 1-3” of antigen presentation (antigen receptor, co-stimulation, cytokines) as perceived by each T cell clone. Given that these signals integrated at antigen presentation cells have been shown to determine the outcome of Teff and Tmem phenotypes and numbers, this decision must be made at a very early stage. It would appear that the overwhelming expansion of effector T cells and the inability to phenotypically distinguish memory T cells at early time points has masked this important decision point. This does not rule out an effect of repeated stimulation or chronic inflammatory milieu on populations generated in these early stages. Recent studies suggest that Tmem are derived from early Teff, and we suggest that this includes Tem as well as Tcm. Therefore, we propose a testable model for the pathway of differentiation from naïve to memory that suggests that Tem are not fully differentiated effector cells, but derived from central memory T cells as originally suggested by Sallusto et al. in 1999, but much debated since.