Stimulation of human butyrophilin 3 molecules results in negative regulation of cellular immunity
Stimulation of human butyrophilin 3 molecules results in negative regulation of cellular immunity
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DOI：
10.1189/jlb.0309156
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发表时间：
2010-10-01
影响因子：
5.5
通讯作者：
Seo, Naohiro
中科院分区：
文献类型：
--
作者：
Yamashiro, Hiromichi;Yoshizaki, Shinji;Seo, Naohiro
BTN分子由BTN 1、BTN 2三个亚家族组成。和BTN 3，并具有生物调节的有趣特性。虽然BTN 1和BTN 2的生物学意义已逐渐阐明，但由于缺乏适当的激动剂，BTN 3的受体功能仍有待阐明。为了阐明BTN 3在免疫调节中的参与，从BTN 3基因免疫的小鼠产生BTN 3特异性mAb，称为34-7和232-5。对BTN 3分子的细胞外结构域具有特异性的232-5 mAb染色几乎所有人PBMC群体，包括T、NK、NKT和B细胞。值得注意的是，用232-5 mAb处理导致BTN 3A 3分子的磷酸化，导致CD 4（+）和CD 8（+）T细胞以CD 4（+）CD 25（+）Treg细胞非依赖性方式的增殖和细胞因子分泌减弱，证明了232-5 mAb在BTN 3介导的负信号转导中的激动性质。BTN 3分子的细胞表面表达的幅度与淋巴细胞活性负相关，表明BTN 3分子有助于维持免疫系统。总之，我们的发现为BTN 3作为过度细胞免疫反应抑制剂的作用提供了新的见解。J. Leukoc. 88：757-767; 2010.
The BTN molecule consists of three subfamilies, BTN1, BTN2. and BTN3, and possesses interesting properties for biological regulation. Although the biological significance of BTN1 and BTN2 has been progressively clarified, the receptor function of BTN3 remains to be elucidated as a result of the absence of appropriate agonists. To clarify the participation of BTN3 in immune regulation, BTN3-specific mAb, referred to as 34-7 and 232-5, were generated from BTN3 gene-immunized mice. The 232-5 mAb, specific to the extracellular domain of the BTN3 molecule, stained almost all populations of human PBMCs, including T, NK, NKT, and B cells. Notably, treatment with the 232-5 mAb resulted in phosphorylation of BTN3A3 molecules, leading to attenuated proliferation and cytokine secretion by CD4(+) and CD8(+) T cells in a CD4(+) CD25(+) Treg cell-independent manner, demonstrating the agonistic property of the 232-5 mAb in BTN3-mediated negative signal transduction. The magnitude of the cell surface expression of BTN3 molecules correlated inversely with lymphocyte activity, suggesting that BTN3 molecules contribute to the maintenance of the immune system. Taken together, our findings provide new insights for the role of BTN3 as an inhibitor of excessive cellular immune responses. J. Leukoc. Biol. 88: 757-767; 2010.