Innate NKTγδ and NKTαβ cells exert similar functions and compete for a thymic niche

Innate NKTγδ and NKTαβ cells exert similar functions and compete for a thymic niche
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先天 NKTγδ 和 NKTαβ 细胞发挥相似的功能并竞争胸腺生态位

DOI:
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发表时间:
2012
影响因子:
5.4
通讯作者:
L. Boucontet
L. Boucontet
中科院分区:
医学3区
文献类型:
--
作者:
P. Pereira;L. Boucontet

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转录调节因子早幼粒细胞白血病锌指(PLZF)在自然杀伤T(NKT)细胞分化过程中高度表达,对于获得其效应/记忆先天样表型至关重要。用抗PLZF和抗NK1.1 Ab染色,可以定义表型和功能不同的NKT α β和NKT γ δ胸腺细胞的两个亚群:PLZF + NK1.1 −亚群,主要由活化时分泌比IFN-γ更多的IL-4的静止细胞组成,以及表达CD 127、NK1.1和其他NK-细胞标志物的PLZF +/− NK1.1+亚群,在活化时分泌比IL-4更多的IFN-γ,并且含有相当大比例的分裂细胞。NK1.1+群体的大小受到非常严格的调控,NK1.1 + α β和γ δ胸腺细胞竞争胸腺小生境。此外,PLZF+和NK1.1+亚群的相对代表性以品系特异性方式变化,C57 BL/6(B6)小鼠含有更多NK1.1+细胞,(B6 × DBA/2)F1(B6D2F1)小鼠含有更多PLZF+细胞。因此,预期体内NKT细胞的活化导致B6D2F1小鼠分泌的IL-4水平高于B6小鼠。与这种可能性相一致的是,与B6小鼠相比,B6D2F1小鼠含有更多的"先天性" CD8+胸腺细胞,其产生取决于NKT细胞分泌的IL-4。
The transcriptional regulator promyelocytic leukemia zinc finger (PLZF) is highly expressed during the differentiation of natural killer T (NKT) cells and is essential for the acquisition of their effector/memory innate‐like phenotype. Staining with anti‐PLZF and anti‐NK1.1 Abs allows the definition of two subsets of NKTαβ and NKTγδ thymocytes that differ phenotypically and functionally: a PLZF+NK1.1− subset composed of mostly quiescent cells that secrete more IL‐4 than IFN‐γ upon activation and a PLZF+/−NK1.1+ subset that expresses CD127, NK1.1, and other NK‐cell markers, secrete more IFN‐γ than IL‐4 upon activation and contains a sizable fraction of dividing cells. The size of the NK1.1+ population is very tightly regulated and NK1.1+ αβ and γδ thymocytes compete for a thymic niche. Furthermore, the relative representation of the PLZF+ and NK1.1+ subsets varies in a strain‐specific manner with C57BL/6 (B6) mice containing more NK1.1+ cells and (B6 × DBA/2)F1 (B6D2F1) mice more PLZF+ cells. Consequently, activation of NKT cells in vivo is expected to result in higher levels of IL‐4 secreted in B6D2F1 mice than in B6 mice. Consistent with this possibility, B6D2F1 mice, when compared with B6 mice, contain more “innate” CD8+ thymocytes, the generation of which depends on IL‐4 secreted by NKT cells.
转录因子 PLZF 指导 NKT 细胞谱系的效应程序。
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