IFN-γ–Producing and IL-17–Producing γδ T Cells Differentiate at Distinct Developmental Stages in Murine Fetal Thymus
IFN-γ–Producing and IL-17–Producing γδ T Cells Differentiate at Distinct Developmental Stages in Murine Fetal Thymus
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DOI：
10.4049/jimmunol.1302145
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发表时间：
2014-03
期刊：
影响因子：
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通讯作者：
K. Shibata;H. Yamada;Masataka Nakamura;S. Hatano;Y. Katsuragi;R. Kominami;Y. Yoshikai
中科院分区：
文献类型：
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作者：
K. Shibata;H. Yamada;Masataka Nakamura;S. Hatano;Y. Katsuragi;R. Kominami;Y. Yoshikai
γδ T细胞在双阴性（DN）2和DN 3阶段发育，并在胎儿胸腺中获得产生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，尽管产生IFN-γ和产生IL-17的γδ T细胞是从DN 2细胞发育而来的，但只有产生IFN-γ的γδ T细胞是从DN 3细胞发育而来的，这表明产生IL-17的γδ T细胞是从DN 2阶段直接产生的，而不是通过DN 3阶段。单细胞分析显示，DN 2细胞含有异质性γδ T细胞前体，具有或不具有产生IL-17的能力。灭活B细胞白血病/淋巴瘤11 B b（一种负责DN 2细胞从早期向晚期转变的锌指转录因子）完全消除了产生IL-17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产生IFN-γ的γδ T细胞的独特亚群能够发育。因此，我们的研究结果表明，γδ T细胞在胎儿胸腺的不同发育阶段功能分化为IFN-γ和IL-17生产者。
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.