Institute of Physiology, Saarland University, Homburg, Germany.
Eur J Immunol. 2012 Feb;42(2):470-5. doi: 10.1002/eji.201141915. Epub 2012 Jan 5.
The major function of cytotoxic T lymphocytes (CTLs) is to eliminate pathogen-infected and tumorigenic cells. This is mediated mainly through the exocytosis of lytic granules (LGs) containing cytotoxic components, such as perforin and granzymes at the immunological synapse (IS). The soluble NSF attachment receptor (SNARE) protein isoforms are well known to be required for vesicle exocytosis in neuronal synapses, but their potential function in CTLs is only partly understood. Here, we examined the expression of SNARE proteins before and after the activation of primary human CD8(+) T cells and determined their co-localization with LGs and CD3 after IS formation with target cells. We found that several key SNARE proteins in neuronal cells were not expressed in CTLs, such as syntaxin1B2 and SNAP-25. Vti1b, Stx8 and Stx16 had the highest degrees of co-localization with LGs while Stx3, Stx4, Stx6, Stx7, Stx8, Stx13, Vti1b, VAMP3 and VAMP4 co-localized with CD3. Our data provide the first complete expression profile and localization of SNAREs in primary human CD8(+) T cells, laying the groundwork for further understanding their potential role in T-cell function.
细胞毒性 T 淋巴细胞 (CTL) 的主要功能是消除被病原体感染和癌变的细胞。这主要是通过在免疫突触 (IS) 中细胞毒性成分的溶酶体颗粒 (LGs) 的胞吐作用来介导的,这些成分包括穿孔素和颗粒酶。可溶性 NSF 附着受体 (SNARE) 蛋白异构体对于神经元突触中的囊泡胞吐作用是众所周知的必需的,但它们在 CTL 中的潜在功能仅部分被理解。在这里,我们研究了人原代 CD8(+) T 细胞活化前后 SNARE 蛋白的表达情况,并确定了它们在与靶细胞形成 IS 后与 LGs 和 CD3 的共定位。我们发现神经元细胞中的几种关键 SNARE 蛋白在 CTL 中不表达,例如 syntaxin1B2 和 SNAP-25。Vti1b、Stx8 和 Stx16 与 LGs 的共定位程度最高,而 Stx3、Stx4、Stx6、Stx7、Stx8、Stx13、Vti1b、VAMP3 和 VAMP4 与 CD3 共定位。我们的数据提供了人原代 CD8(+) T 细胞中 SNARE 表达的完整图谱和定位,为进一步了解它们在 T 细胞功能中的潜在作用奠定了基础。