CD8αβ+ γδ T Cells: A Novel T Cell Subset with a Potential Role in Inflammatory Bowel Disease
CD8αβ+ γδ T Cells: A Novel T Cell Subset with a Potential Role in Inflammatory Bowel Disease
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DOI：
10.4049/jimmunol.1601146
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发表时间：
2016-12-15
影响因子：
4.4
通讯作者：
Marsal, Jan
中科院分区：
文献类型：
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作者：
Kadivar, Mohammad;Petersson, Julia;Marsal, Jan
γδT 细胞具有多种功能，但在某些情况下可能显得相互矛盾。为了更好地了解 γδT 细胞的神秘生物学，定义其亚群至关重要。此前，γ δ T 细胞被分为两个亚群：CD8 α α(+) 和 CD8 细胞。在这项研究中，我们定义并表征了表达 CD8 α β 的人类 γ δ T 细胞的新子集。这些 CD8 α beta(+) γ δ T 细胞在几个方面与之前描述的 γ δ T 细胞亚群不同，包括肠粘膜内的富集程度、血液中的激活状态、血液中使用的 TCR δ 变体的类型，以及它们对 IL-2 刺激的反应的微小但显着的差异。此外，新的亚群表达细胞毒性介质和 CD69，并产生 IFN-γ 和 TNF-α。在患有活动性炎症性肠病的患者中，与健康对照相比，粘膜中CD8αβ(+)gdT细胞的频率显着降低，与疾病活动程度呈负相关，并且由于抗TNF-α治疗而增加至正常水平。总之，我们的结果表明，CD8αβ(+)γδT细胞构成了一种新的淋巴细胞亚群，该亚群在肠道内大量富集，可能在炎症性肠病的肠道稳态和粘膜愈合中发挥重要作用。
gamma delta T cells have been attributed a wide variety of functions, which in some cases may appear as contradictory. To better understand the enigmatic biology of gamma delta T cells it is crucial to define the constituting subpopulations. gamma delta T cells have previously been categorized into two subpopulations: CD8 alpha alpha(+) and CD8-cells. In this study we have defined and characterized a novel subset of human gamma delta T-cells expressing CD8 alpha beta. These CD8 alpha beta(+) gamma delta T cells differed from the previously described gamma delta T cell subsets in several aspects, including the degree of enrichment within the gut mucosa, the activation status in blood, the type of TCR delta variant used in blood, and small but significant differences in their response to IL-2 stimulation. Furthermore, the novel subset expressed cytotoxic mediators and CD69, and produced IFN-gamma and TNF-alpha. In patients with active inflammatory bowel disease the mucosal frequencies of CD8 alpha beta(+) gd T cells were significantly lower as compared with healthy controls, correlated negatively with the degree of disease activity, and increased to normal levels as a result of anti-TNF-alpha therapy. In conclusion, our results demonstrate that CD8 alpha beta(+) gamma delta T cells constitute a novel lymphocyte subset, which is strongly enriched within the gut and may play an important role in gut homeostasis and mucosal healing in inflammatory bowel disease.