Division of Host Defense, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
J Immunol. 2014 Mar 1;192(5):2210-8. doi: 10.4049/jimmunol.1302145. Epub 2014 Jan 31.
γδ T cells develop at the double-negative (DN) 2 and DN3 stages and acquire functions to produce IL-17 and IFN-γ in fetal thymus. However, the relationship between differentiation stages and their functions was unclear. In this study, we found that, although IFN-γ-producing and IL-17-producing γδ T cells developed from DN2 cells, only IFN-γ-producing γδ T cells developed from DN3 cells, indicating the direct generation of IL-17-producing γδ T cells from the DN2 stage, not through the DN3 stage. Single-cell analysis revealed that DN2 cells contained heterogeneous γδ T cell precursors with or without an ability to develop IL-17 producers. Inactivation of B cell leukemia/lymphoma 11b, a zinc finger transcription factor responsible for transition from early to late stages of DN2 cells, completely abrogated the development of IL-17-producing γδ T cells, although a unique subset of IFN-γ-producing γδ T cells expressing a high level of promyelocytic leukemia zinc finger was able to develop. Thus, our results reveal that γδ T cells are functionally differentiated to IFN-γ and IL-17 producers at different developmental stages in fetal thymus.
γδ T 细胞在双阴性 (DN) 2 和 DN3 阶段发育，并在胎胸腺中获得产生 IL-17 和 IFN-γ 的功能。然而，分化阶段与其功能之间的关系尚不清楚。在这项研究中，我们发现，虽然 IFN-γ 产生和 IL-17 产生的 γδ T 细胞来自 DN2 细胞，但只有 IFN-γ 产生的 γδ T 细胞来自 DN3 细胞，这表明 IL-17 产生的 γδ T 细胞直接从 DN2 阶段产生，而不是通过 DN3 阶段。单细胞分析表明，DN2 细胞包含具有或不具有产生 IL-17 能力的异质性 γδ T 细胞前体。B 细胞白血病/淋巴瘤 11b 的失活，一种锌指转录因子，负责从 DN2 细胞的早期向晚期的过渡，完全阻断了 IL-17 产生的 γδ T 细胞的发育，尽管表达高水平早幼粒细胞白血病锌指的独特 IFN-γ 产生的 γδ T 细胞亚群能够发育。因此，我们的结果表明，在胎胸腺中，γδ T 细胞在不同的发育阶段向 IFN-γ 和 IL-17 产生者分化。
