<br>表达 HELIOS 的人类 CD8 T 细胞表现出有限的效应功能,Frontiers in Immunology

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表达 HELIOS 的人类 CD8 T 细胞表现出有限的效应功能
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2023-12-22 , DOI: 10.3389/fimmu.2023.1308539
Damien Neyens ₁ , Thibault Hirsch ₁ , Achraqat Abdel Aziz Issa Abdel Hadi ₁ , Nicolas Dauguet ₁ , Christophe Vanhaver ₁ , Alexandre Bayard ₁ , Claude Wildmann ₁ , Mathieu Luyckx _{1,

2} , Jean-Luc Squifflet _{1,

2} , Quentin D'Hondt ₁ , Céline Duhamel ₁ , Antoine Huaux ₁ , Virginie Montiel ₃ , Mélanie Dechamps ₃ , Pierre van der Bruggen _{1,

4}

Affiliation

简介转录因子 HELIOS 主要因其在人类和小鼠 CD4 调节性 T 细胞中的表达而闻名。在小鼠体内，HELIOS 存在于耗尽的 CD8 T 细胞中。然而，关于人类赫利俄斯的信息+ CD8 T 细胞是有限且相互矛盾的。方法在本研究中，我们通过流式细胞术和转录组分析人类 HELIOS 进行表征+ CD8 T 细胞。结果这些 T 细胞主要由记忆细胞组成，约占血液 CD8 T 细胞的 21%。与内存 HELIOS 相比- T-BET高的CD8 T 细胞表现出强大的效应功能，即记忆 HELIOS + T-BET高的CD8 T 细胞产生较低量的 IFN-γ 和 TNF-α，并且具有较低的细胞毒性潜力。我们想知道这些细胞是否参与针对病毒抗原的免疫反应，但没有发现 HELIOS + CD8 T 细胞中识别 HLA-A2 和 HLA-B7 呈递的 CMV 肽的细胞。然而，我们发现了赫利俄斯+ CD8 T 细胞识别 MHC Ib 类分子 HLA-E 呈递的 CMV 肽。此外，HELIOS 的一部分+ CD8 T 细胞的特点是表达 CD161，通常用作识别 T 细胞的表面标记C17细胞。这些 CD8 T 细胞表达 T H17 /T C17编码 RORgt、RORa、PLZF 和 CCL20 的相关基因。讨论我们的研究结果强调，HELIOS 在各种 CD8 T 细胞群体中表达，强调其重要性超出了其作为 Treg 或耗竭的鼠 CD8 T 细胞转录因子的作用。 HELIOS 和 HLA-E 限制之间联系的重要性尚不清楚。

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HELIOS-expressing human CD8 T cells exhibit limited effector functions

IntroductionThe transcription factor HELIOS is primarily known for its expression in CD4 regulatory T cells, both in humans and mice. In mice, HELIOS is found in exhausted CD8 T cells. However, information on human HELIOS+ CD8 T cells is limited and conflicting.MethodsIn this study, we characterized by flow cytometry and transcriptomic analyses human HELIOS+ CD8 T cells.ResultsThese T cells primarily consist of memory cells and constitute approximately 21% of blood CD8 T cells. In comparison with memory HELIOS- T-BEThigh CD8 T cells that displayed robust effector functions, the memory HELIOS+ T-BEThigh CD8 T cells produce lower amounts of IFN-γ and TNF-α and have a lower cytotoxic potential. We wondered if these cells participate in the immune response against viral antigens, but did not find HELIOS+ cells among CD8 T cells recognizing CMV peptides presented by HLA-A2 and HLA-B7. However, we found HELIOS+ CD8 T cells that recognize a CMV peptide presented by MHC class Ib molecule HLA-E. Additionally, a portion of HELIOS+ CD8 T cells is characterized by the expression of CD161, often used as a surface marker for identifying TC17 cells. These CD8 T cells express TH17/TC17-related genes encoding RORgt, RORa, PLZF, and CCL20.DiscussionOur findings emphasize that HELIOS is expressed across various CD8 T cell populations, highlighting its significance beyond its role as a transcription factor for Treg or exhausted murine CD8 T cells. The significance of the connection between HELIOS and HLA-E restriction is yet to be understood.

更新日期：2023-12-22

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