Activated T helper 1 and T helper 2 cells differentially express the beta-2-adrenergic receptor: a mechanism for selective modulation of T helper 1 cell cytokine production.
Activated T helper 1 and T helper 2 cells differentially express the beta-2-adrenergic receptor: a mechanism for selective modulation of T helper 1 cell cytokine production.
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DOI：
10.4049/jimmunol.159.10.4857
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发表时间：
1997-11
影响因子：
4.4
通讯作者：
D. Ramer-Quinn;R. A. Baker;Virginia M. Sanders
中科院分区：
文献类型：
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作者：
D. Ramer-Quinn;R. A. Baker;Virginia M. Sanders
我们最近报道，静息的小鼠Th1细胞克隆，但不表达静息的Th2细胞，表达可检测到的β2肾上腺素能受体(β2AR)。在本研究中，我们认为抗CD3单抗激活的CD4+效应Th细胞上β2AR的表达水平可能与静止细胞上的水平不同，并且受体表达的变化可能改变这些细胞对β2AR选择性配体特布他林或交感神经递质去甲肾上腺素的功能反应性。在抗CD3激活后，β2AR在Th1细胞上表达，但在Th2细胞上不表达。在24小时的激活期内，Th1细胞上的结合位点数量保持不变，亲和力没有变化。当Th克隆在抗CD3激活后暴露于特布他林时，Th1细胞，而不是Th2细胞，细胞因子的产生被调节。Th1细胞产生IL-2减少，而产生干扰素-γ无明显变化。IL-2产生的减少呈浓度依赖关系，并可被拮抗剂阻断。与对照上清液相比，特布他林处理的培养上清液中IL-2水平较低，对依赖IL-2的Th1克隆的增殖有较小的支持作用。此外，去甲肾上腺素通过与β-肾上腺素能受体特异性结合，下调IL-2的产生，但不下调干扰素-γ的产生。因此，可检测到的β2AR水平在激活的Th1细胞上表达，但不在激活的Th2细胞上表达，从而提供了一种机制，通过该机制，IL-2的产生优先受到Th1细胞激活后的内源性和治疗性配体的调节。
We recently reported that resting clones of murine Th1 cells, but not resting Th2 cells, expressed a detectable level of the beta-2-adrenergic receptor (beta 2AR). In the present study, we proposed that the level of beta 2AR expression on anti-CD3 mAb-activated CD4+ effector Th cells may differ from the level on resting cells, and that a change in receptor expression may alter the functional responsiveness of these cells to either the beta 2AR-selective ligand terbutaline or the sympathetic neurotransmitter norepinephrine. Following anti-CD3 activation, the beta 2AR was expressed on Th1 cells, but not Th2 cells. The number of binding sites on Th1 cells was maintained, with no change in affinity, over a 24-h activation period. When Th clones were exposed to terbutaline following anti-CD3 activation, Th1 cell, but not Th2 cell, cytokine production was modulated. IL-2 production by Th1 cells was decreased, while IFN-gamma production was not significantly altered. The decrease in IL-2 production was concentration dependent and was blocked by an antagonist. In comparison with control supernatants, the lower level of IL-2 present in terbutaline-exposed culture supernatants supported the proliferation of an IL-2-dependent Th1 clone to a lesser degree. Additionally, norepinephrine down-modulates IL-2, but not IFN-gamma, production by binding specifically to the beta-adrenergic receptor. Thus, a detectable level of the beta 2AR is expressed on activated Th1 cells, but not activated Th2 cells, thereby providing a mechanism by which IL-2 production is preferentially modulated by an endogenous and therapeutic ligand following Th1 cell activation.