Äijö Tarmo, Gioulbasani Marianthi, Valenzuela Jair Ernesto, Tsagaratou Ageliki
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Front Immunol. 2025 Aug 20;16:1638500. doi: 10.3389/fimmu.2025.1638500. eCollection 2025.
Ten Eleven Translocation (TET) proteins can oxidize 5-methylcytosine to generate in sequential steps oxidized forms of cytosine: 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine. Through their catalytic activity TET proteins promote active DNA demethylation. There are three TET proteins: TET1, TET2 and TET3. In T cells, TET2 and TET3 are more highly expressed. In the past years we have extensively analyzed the impact of TET proteins and 5-hydroxymethylcytosine in T cell development. In this report, we focus on the impact of TET proteins in the TCR alpha (α) and beta (β) repertoires in thymic CD4 single positive cells and upon migration in the periphery. Our data reveal that both wild type and DKO CD4 cells in the thymus and the spleen are polyclonal. Then, we focus on DKO CD4 cells that are serially transplanted in recipient mice. Our TCR sequencing data reveals that expanded DKO CD4 cells are less diverse and oligoclonal. Overall, this report serves as a resource of TCRα and TCRβ repertoire in both wild type and DKO murine conventional CD4 T cells and provides insights on how expanded DKO CD4 cells opt for specific TCRα and β repertoires.
十一易位（TET）蛋白可将5-甲基胞嘧啶氧化，依次生成胞嘧啶的氧化形式：5-羟甲基胞嘧啶、5-甲酰基胞嘧啶和5-羧基胞嘧啶。通过其催化活性，TET蛋白促进DNA的主动去甲基化。有三种TET蛋白：TET1、TET2和TET3。在T细胞中，TET2和TET3的表达水平更高。在过去几年中，我们广泛分析了TET蛋白和5-羟甲基胞嘧啶在T细胞发育中的影响。在本报告中，我们重点关注TET蛋白对胸腺CD4单阳性细胞以及在外周迁移过程中TCRα和TCRβ库的影响。我们的数据显示，胸腺和脾脏中的野生型和双敲除（DKO）CD4细胞都是多克隆的。然后，我们重点研究了在受体小鼠中连续移植的DKO CD4细胞。我们的TCR测序数据显示，扩增的DKO CD4细胞多样性较低且为寡克隆性。总体而言，本报告提供了野生型和DKO小鼠传统CD4 T细胞中TCRα和TCRβ库的相关信息，并深入探讨了扩增的DKO CD4细胞如何选择特定的TCRα和β库。
