Institute of Immunology, University of Kiel, Kiel, Germany.
Scand J Immunol. 2012 Sep;76(3):213-22. doi: 10.1111/j.1365-3083.2012.02727.x.
The dominant subset of γδ T cells in human peripheral blood expresses Vγ9 paired with Vδ2 as variable TCR elements. Vγ9Vδ2 T cells recognize pyrophosphates derived from the microbial non-mevalonate isoprenoid biosynthesis pathway at pico- to nanomolar concentrations. Structurally related pyrophosphates are generated in eukaryotic cells through the mevalonate pathway involved in protein prenylation and cholesterol synthesis. However, micromolar concentrations of endogenous pyrophosphates are required to be recognized by Vγ9Vδ2 T cells. Such concentrations are not produced by normal cells but can accumulate upon cellular stress and transformation. Therefore, many tumour cells are susceptible to γδ T cell-mediated lysis owing to the overproduction of endogenous pyrophosphates. This explains why Vγ9Vδ2 T cells contribute to both anti-infective and anti-tumour immunity. Ex vivo analysed Vγ9Vδ2 T cells can be subdivided on the basis of additional surface markers, including chemokine receptors and markers for naïve and memory T cells. At the functional level, Vγ9Vδ2 T cells produce a broad range of cytokines, display potent cytotoxic activity, regulate αβ T cell responses, and - quite surprisingly - can act as professional antigen-presenting cells. Thus, an exceptional range of effector functions has been assigned to a population of T cells, which all recognize invariant exogenous or endogenous pyrophosphates that are not seen by any other immune cell. Here, we discuss whether this plethora of effector functions reflects the plasticity of individual Vγ9Vδ2 T cells or can be assigned to distinct subsets.
人外周血中占主导地位的 γδ T 细胞亚群表达 Vγ9 与 Vδ2 作为可变 TCR 元件。Vγ9Vδ2 T 细胞以皮摩尔至纳摩尔浓度识别微生物非甲羟戊酸异戊烯基生物合成途径衍生的焦磷酸盐。结构上相关的焦磷酸盐通过涉及蛋白异戊烯化和胆固醇合成的甲羟戊酸途径在真核细胞中产生。然而，Vγ9Vδ2 T 细胞需要识别内源性焦磷酸盐的微摩尔浓度。这些浓度不是正常细胞产生的，但在细胞应激和转化时会积累。因此，由于内源性焦磷酸盐的过度产生，许多肿瘤细胞容易受到 γδ T 细胞介导的裂解。这解释了为什么 Vγ9Vδ2 T 细胞有助于抗感染和抗肿瘤免疫。体外分析的 Vγ9Vδ2 T 细胞可以根据其他表面标志物进一步细分，包括趋化因子受体以及幼稚和记忆 T 细胞的标志物。在功能水平上，Vγ9Vδ2 T 细胞产生广泛的细胞因子，显示出强大的细胞毒性活性，调节 αβ T 细胞反应，并且 - 非常令人惊讶的是 - 可以作为专业的抗原呈递细胞。因此，已经赋予了一群 T 细胞一系列特殊的效应功能，这些 T 细胞都识别不变的外源性或内源性焦磷酸盐，而其他免疫细胞则无法识别。在这里，我们讨论这些众多的效应功能是否反映了个体 Vγ9Vδ2 T 细胞的可塑性，或者可以分配给不同的亚群。
