Canine tissue-associated CD4+CD8α+ double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential
Canine tissue-associated CD4+CD8α+ double-positive T cells are an activated T cell subpopulation with heterogeneous functional potential
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DOI：
10.1371/journal.pone.0213597
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发表时间：
2019-03-13
期刊：
影响因子：
3.7
通讯作者：
Eschke, Maria
中科院分区：
文献类型：
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作者：
Rabiger, Friederike V.;Bismarck, Doris;Eschke, Maria
犬外周血CD 4（+）CD 8 α（+）双阳性（dp）T细胞是一种独特的效应记忆T细胞亚群，其特征是与常规CD 4（+）或CD 8 α（+）单阳性（sp）T细胞相比，活化标志物的表达增加。在这项研究中，我们通过多色流式细胞术研究了一组同质健康比格犬次级淋巴器官（即肠系膜和气管支气管淋巴结、脾脏、派伊尔集合淋巴结）和非淋巴组织（即肺和小肠上皮）中的CD 4（+）CD 8 α（+）dp T细胞。该系统分析的目的是确定这种不同T细胞亚群的组织特异性定位和特征。我们的研究结果显示，在所有分析的器官中，胸腺外成熟的CD 1a（-）CD 4（+）CD 8 α（+）dp T细胞群，在派尔集合淋巴结中的频率最高。活化标志物CD 25的组成型表达是许多CD 4（+）CD 8 α（+）dp T细胞的特征，与其定位无关，并指向效应表型。淋巴结CD 4（+）CD 8 α（+）dp T细胞的比例为FoxP 3（+），表明具有调节潜力。在肠道环境中，细胞毒性标记物颗粒酶B由CD 4（+）CD 8 α（+）dp上皮内淋巴细胞表达。此外，CD 4（+）CD 8 α（+）dp上皮内淋巴细胞和肠系膜淋巴结CD 4（+）CD 8 α（+）dp T细胞的一部分是TCR γ δ（+）。然而，所有组织相关的CD 4（+）CD 8 α（+）dp T细胞的主要T细胞受体可以被鉴定为TCR α β。有趣的是，与主要为CD 8 α β（+）的CD 8 α（+）sp T细胞和CD 4（+）CD 8 α + dp胸腺细胞相反，大多数CD 4（+）CD 8 α（+）dp T细胞亚群表达非常规的CD 8 α α同源二聚体。所提供的数据为组织特异性CD 4（+）CD 8 α（+）dp T细胞的功能分析提供了基础，以阐明它们在犬的健康和疾病中的作用。
Canine CD4(+)CD8 alpha(+) double-positive (dp) T cells of peripheral blood are a unique effector memory T cell subpopulation characterized by an increased expression of activation markers in comparison with conventional CD4(+) or CD8 alpha(+) single-positive (sp) T cells. In this study, we investigated CD4(+)CD8 alpha(+) dp T cells in secondary lymphatic organs (i.e. mesenteric and tracheobronchial lymph nodes, spleen, Peyer's patches) and non-lymphatic tissues (i.e. lung and epithelium of the small intestine) within a homogeneous group of healthy Beagle dogs by multi-color flow cytometry. The aim of this systematic analysis was to identify the tissue-specific localization and characteristics of this distinct T cell subpopulation. Our results revealed a mature extrathymic CD1a(-)CD4(+)CD8 alpha(+) dp T cell population in all analyzed organs, with highest frequencies within Peyer's patches. Constitutive expression of the activation marker CD25 is a feature of many CD4(+)CD8 alpha(+) dp T cells independent of their localization and points to an effector phenotype. A proportion of lymph node CD4(+)CD8 alpha(+) dp T cells is FoxP3(+) indicating regulatory potential. Within the intestinal environment, the cytotoxic marker granzyme B is expressed by CD4(+)CD8 alpha(+) dp intraepithelial lymphocytes. In addition, a fraction of CD4(+)CD8 alpha(+) dp intraepithelial lymphocytes and of mesenteric lymph node CD4(+)CD8 alpha(+) dp T cells is TCR gamma delta(+). However, the main T cell receptor of all tissue-associated CD4(+)CD8 alpha(+) dp T cells could be identified as TCR alpha beta. Interestingly, the majority of the CD4(+)CD8 alpha(+) dp T cell subpopulation expresses the unconventional CD8 alpha alpha homodimer, in contrast to CD8 alpha(+) sp T cells, and CD4(+)CD8 alpha+ dp thymocytes which are mainly CD8 alpha beta(+). The presented data provide the basis for a functional analysis of tissue-specific CD4(+)CD8 alpha(+) dp T cells to elucidate their role in health and disease of dogs.