CD70 defines a subset of proinflammatory and CNS-pathogenic TH1/TH17 lymphocytes and is overexpressed in multiple sclerosis.,Cellular & Molecular Immunology

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CD70 defines a subset of proinflammatory and CNS-pathogenic TH1/TH17 lymphocytes and is overexpressed in multiple sclerosis.
Cellular & Molecular Immunology ( IF 21.8 ) Pub Date : 2019-01-11 , DOI: 10.1038/s41423-018-0198-5
Tessa Dhaeze ₁ , Laurence Tremblay ₁ , Catherine Lachance ₁ , Evelyn Peelen ₁ , Stephanie Zandee ₁ , Camille Grasmuck ₁ , Lyne Bourbonnière ₁ , Sandra Larouche ₁ , Xavier Ayrignac _{1,

2} , Rose-Marie Rébillard ₁ , Josée Poirier ₂ , Boaz Lahav ₂ , Pierre Duquette _{1,

2} , Marc Girard _{1,

2} , Robert Moumdjian ₃ , Alain Bouthillier ₃ , Catherine Larochelle _{1,

2} , Alexandre Prat _{1,

2}

Affiliation

CD70 is the unique ligand of CD27 and is expressed on immune cells only upon activation. Therefore, engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of CD70. However, the T cell-intrinsic effect and function of human CD70 remain underexplored. Herein, we describe that CD70 expression distinguishes proinflammatory CD4+ T lymphocytes that display an increased potential to migrate into the central nervous system (CNS). Upregulation of CD70 on CD4+ T lymphocytes is induced by TGF-β1 and TGF-β3, which promote a pathogenic phenotype. In addition, CD70 is associated with a TH1 and TH17 profile of lymphocytes and is important for T-bet and IFN-γ expression by both T helper subtypes. Moreover, adoptive transfer of CD70-/-CD4+ T lymphocytes induced less severe experimental autoimmune encephalomyelitis (EAE) disease than transfer of WT CD4+ T lymphocytes. CD70+CD4+ T lymphocytes are found in the CNS during acute autoimmune inflammation in humans and mice, highlighting CD70 as both an immune marker and an important costimulator of highly pathogenic proinflammatory TH1/TH17 lymphocytes infiltrating the CNS.

中文翻译：

CD70定义了促炎性和CNS致病性TH1 / TH17淋巴细胞的子集，并且在多发性硬化症中过表达。

CD70是CD27的独特配体，仅在激活时才在免疫细胞上表达。因此，共刺激CD27 / CD70途径的参与完全取决于CD70的上调。然而，人类CD70的T细胞内在作用和功能仍未得到充分研究。在本文中，我们描述了CD70的表达区别了促炎性CD4 + T淋巴细胞，后者显示出迁移到中枢神经系统（CNS）的潜力。TGF-β1和TGF-β3诱导CD4 + T淋巴细胞上CD70的上调，这促进了致病表型。此外，CD70与淋巴细胞的TH1和TH17谱相关，并且对于两种T辅助亚型的T-bet和IFN-γ表达都很重要。而且，CD70-/-CD4 + T淋巴细胞的过继转移诱导的实验性自身免疫性脑脊髓炎（EAE）疾病的严重程度低于WT CD4 + T淋巴细胞的转移。在人类和小鼠的急性自身免疫炎症期间，在CNS中发现了CD70 + CD4 + T淋巴细胞，这突显了CD70作为高致病性促炎性TH1 / TH17淋巴细胞浸润到CNS中的一种免疫标记和重要的共刺激物。

更新日期：2019-05-16

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