Identification of Chicken GITR and GITR Ligand, Proof of Their Mutual Interaction, and Analysis of Chicken GITR Tissue Distribution by a Novel Antibody That Reveals Expression on Activated T Cells and Erythrocytes
Identification of Chicken GITR and GITR Ligand, Proof of Their Mutual Interaction, and Analysis of Chicken GITR Tissue Distribution by a Novel Antibody That Reveals Expression on Activated T Cells and Erythrocytes
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DOI：
10.4049/immunohorizons.1800065
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发表时间：
2018-11
期刊：
影响因子：
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通讯作者：
S. Scherer;Daniela Huhle;T. Göbel
中科院分区：
文献类型：
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作者：
S. Scherer;Daniela Huhle;T. Göbel
糖皮质激素诱导的TNFR（GITR）及其配体GITRL属于TNF超家族的共刺激成员，并且关键地参与有效免疫应答的形成和调节，包括先天性和适应性机制。在这项研究中，我们确定和描述鸡GITR和GITRL，并提供了新开发的chGITR特异性mAb 9 C5的初步表征。推定的鸡分子GITR和GITRL的结构分析证实保守的经典拓扑结构特征与它们的哺乳动物同源物相比，并建议相互作用的能力，这是通过流式细胞术验证。尽管仅从脾、囊和胸腺分离的天然淋巴细胞的微小群体表达GITR，但其在αβ和γδ T细胞（包括CD 4+以及CD 8+亚群）上活化后强烈上调。在血液中，一部分CD 4 + CD 25 + T细胞组成型表达GITR。此外，几乎所有鸡红细胞都显示出高水平的GITR。我们的研究结果验证了鸡中GITR及其配体GITRL的存在;它们提供了进一步表征其在免疫应答中的影响的基础和新工具，并揭示了红细胞上GITR迄今未被识别的表达。
Glucocorticoid-induced TNFR (GITR) and its ligand, GITRL, belong to the costimulatory members of the TNF superfamily and are crucially involved in the formation and modulation of an effective immune response, comprising innate as well as adaptive mechanisms. In this study, we identify and describe chicken GITR and GITRL, and provide an initial characterization of the newly developed chGITR-specific mAb 9C5. Structural analyses of the putative chicken molecules GITR and GITRL confirmed the conservation of classic topological features compared with their mammalian homologs and suggested the ability of mutual interaction, which was verified via flow cytometry. Whereas only minute populations of native lymphocytes isolated from spleen, bursa, and thymus expressed GITR, it was strongly upregulated upon activation on αβ and γδ T cells, comprising CD4+ as well as CD8+ subsets. In blood, a fraction of CD4+CD25+ T cells constitutively expressed GITR. In addition, virtually all chicken erythrocytes displayed high levels of GITR. Our results verify the existence of both GITR and its ligand, GITRL, in chickens; they provide the basis and novel tools to further characterize their impact within the immune response and reveal the so-far unrecognized expression of GITR on erythrocytes.