TCR-α/β CD4- CD8- double negative T cells arise from CD8+ T cells.,Journal of Leukocyte Biology

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TCR-α/β CD4- CD8- double negative T cells arise from CD8+ T cells.
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2020-02-13 , DOI: 10.1002/jlb.1ab0120-548r
Noé Rodríguez-Rodríguez _{1,

2,

3} , Giovanna Flores-Mendoza ₂ , Sokratis A Apostolidis _{1,

4} , Florencia Rosetti ₂ , George C Tsokos ₁ , José C Crispín _{1,

2,

5}

Affiliation

The cellular origin of CD4⁻ CD8⁻ (double negative, DNT) TCR‐α/β⁺ T cells remains unknown. Available evidence indicates that they may derive from CD8⁺ T cells, but most published data have been obtained using cells that bear an invariant transgenic T cell receptor that recognizes an Ag that is not present in normal mice. Here, we have used complementary fate mapping and adoptive transfer experiments to identify the cellular lineage of origin of DNT cells in wild‐type mice with a polyclonal T cell repertoire. We show that TCR‐α/β⁺ DNT cells can be traced back to CD8⁺ and CD4⁺CD8⁺ double positive cells in the thymus. We also demonstrate that polyclonal DNT cells generated in secondary lymphoid organs proliferate upon adoptive transfer and can regain CD8 expression in lymphopenic environment. These results demonstrate the cellular origin of DNT cells and provide a conceptual framework to understand their presence in pathological circumstances.

中文翻译：

TCR-α/βCD4- CD8-双阴性T细胞来自CD8 + T细胞。

CD4的细胞来源^- CD8 ^-（双阴性，DNT）TCR-α/β ⁺ T细胞仍然是未知的。现有证据表明它们可能源自CD8 ⁺ T细胞，但是大多数发表的数据是使用携带不变的转基因T细胞受体的细胞获得的，该受体识别正常小鼠中不存在的Ag。在这里，我们使用了互补的命运作图法和过继转移实验来鉴定具有多克隆T细胞库的野生型小鼠中DNT细胞来源的细胞谱系。我们显示TCR‐α /β ⁺ DNT细胞可以追溯到CD8 ⁺和CD4 ⁺ CD8 ⁺胸腺中有双阳性细胞。我们还证明了在继发性淋巴器官中产生的多克隆DNT细胞在过继转移时增殖，并且可以在淋巴细胞减少的环境中恢复CD8的表达。这些结果证明了DNT细胞的细胞起源，并提供了一个概念框架来了解其在病理情况下的存在。

更新日期：2020-02-13

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