The cytolytic enzymes granyzme A, granzyme B, and perforin: expression patterns, cell distribution, and their relationship to cell maturity and bright CD57 expression
The cytolytic enzymes granyzme A, granzyme B, and perforin: expression patterns, cell distribution, and their relationship to cell maturity and bright CD57 expression
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DOI：
10.1189/jlb.0208107
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发表时间：
2009-01-01
影响因子：
5.5
通讯作者：
De Rosa, Stephen C.
中科院分区：
文献类型：
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作者：
Chattopadhyay, Pratip K.;Betts, Michael R.;De Rosa, Stephen C.
细胞溶解酶（CEs）是抗病毒和抗肿瘤免疫的关键介质，然而，由于许多分子属于这种酶家族，我们对CEs的理解仍然有限。具体而言，目前仍不清楚颗粒酶和穿孔素（Perf）的组合是由各种免疫细胞表达的，以及CE含量如何与细胞分化相关。使用多色流式细胞术，我们同时测量了最常见的人类CE [颗粒酶A（gA）、颗粒酶B（gB）和Perf]以及α β和γ δ T细胞成熟的标志物（CD 45 RO、CCR 7、CD 27、CD 57）的表达。此外，我们测量了NK细胞亚群中的CE含量（由其CD 16和CD 56的表达定义）。我们发现，在各种各样的免疫细胞中，CE含量与细胞成熟度有关。此外，共同的表达模式在细胞类型之间共享，使得gB+细胞总是含有gA，而Perf+细胞主要是gA+ gB+。最重要的是，CD 57表达与gA、gB和Perf的同时表达强烈相关。因此，CD 57的使用提供了一种容易分离具有高细胞溶解潜力的活细胞的方法，而不需要致死固定/透化技术。J. Leukoc. 85：88-97; 2009.
Cytolytic enzymes (CEs) are critical mediators of anti-viral and -tumor immunity; however, as a number of molecules belong to this enzyme family, our understanding of CEs remains limited. Specifically, it remains unclear what combinations of granzymes and perforin (Perf) are expressed by various immune cells and how CE content relates to cellular differentiation. Using polychromatic flow cytometry, we simultaneously measured expression of the most common human CEs [granzyme A (gA), granzyme B (gB), and Perf] alongside markers of alpha beta and gamma delta T cell maturation (CD45RO, CCR7, CD27, CD57). Additionally, we measured CE content in NK cell subsets ( defined by their expression of CD16 and CD56). We found that among a wide variety of immune cells, CE content was linked to cellular maturity. Moreover, common expression patterns were shared across cell types, such that gB+ cells always contained gA, and Perf+ cells were primarily gA+ gB+. Most importantly, CD57 expression correlated strongly with simultaneous expression of gA, gB, and Perf. Thus, the use of CD57 provides a means to easily isolate viable cells with high cytolytic potential, without the need for lethal fixation/permeabilization techniques. J. Leukoc. Biol. 85: 88-97; 2009.