Differential expression of the beta2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help.
Differential expression of the beta2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help.
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DOI：
10.4049/jimmunol.158.9.4200
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发表时间：
1997-05
影响因子：
4.4
通讯作者：
V. Sanders;R. A. Baker;D. Ramer-Quinn;Deborah J. Kasprowicz;B. Fuchs;N. Street
中科院分区：
文献类型：
--
作者：
V. Sanders;R. A. Baker;D. Ramer-Quinn;Deborah J. Kasprowicz;B. Fuchs;N. Street
交感神经系统的一个重要功能是通过调节许多不同器官系统中的细胞活性水平来维持体内平衡。交感神经递质去甲肾上腺素通过与β 2-肾上腺素能受体（β 2 AR）结合来调节T和B淋巴细胞活性的水平。本研究旨在阐明刺激β 2 AR影响Th 1/Th 2细胞细胞因子产生和Th 1/Th 2细胞依赖性Ab产生的机制。小鼠Th 1/Th 2细胞的克隆在被Ag呈递B细胞激活之前暴露于β 2 AR激动剂特布他林。活化前暴露于Th 1细胞的特布他林抑制Th 1细胞产生IFN-γ和随后B细胞产生IgG 2a。通过加入β AR拮抗剂纳多洛尔或外源性IFN-γ防止IgG 2a抑制。与Th 1细胞相反，特布他林不影响Th 2细胞产生IL-4或随后B细胞产生IgG 1。虽然细胞内cAMP的基线水平在两个亚群中相似，但特布他林仅在Th 1细胞中诱导cAMP水平增加。放射性配体结合研究表明，可检测到的β 2 AR结合位点存在于Th 1细胞，但不是在Th 2细胞。免疫荧光分析表明，Th 1细胞表达了更高水平的β 2 AR胞质羧基端比Th 2细胞。这些结果表明，β 2 AR结合位点由Th 1细胞表达，而不是由Th 2细胞表达，建立了选择性调节Th 1细胞IFN-γ产生和IFN-γ依赖性IgG 2 α产生的生理机制，前提是β 2 AR刺激发生在B细胞激活细胞之前。
An important function of the sympathetic nervous system is to maintain homeostasis by modulating the level of cellular activity in many diverse organ systems. The sympathetic neurotransmitter norepinephrine modulates the level of T and B lymphocyte activity by binding to the beta2-adrenergic receptor (beta2AR). The present study was designed to elucidate the mechanism by which stimulation of the beta2AR affects both Th1/Th2 cell cytokine production and Th1/Th2 cell-dependent Ab production. Clones of murine Th1/Th2 cells were exposed to the beta2AR agonist terbutaline before activation by Ag-presenting B cells. Terbutaline exposure of Th1 cells before activation inhibited IFN-gamma production by Th1 cells and subsequent IgG2a production by B cells. IgG2a inhibition was prevented by addition of the betaAR antagonist nadolol or exogenous IFN-gamma. In contrast to Th1 cells, terbutaline did not affect either IL-4 production by Th2 cells or subsequent IgG1 production by B cells. Although baseline levels of intracellular cAMP were similar in both subsets, terbutaline induced an increase in cAMP levels in Th1 cells only. Radioligand binding studies showed that a detectable number of beta2AR binding sites were present on Th1 cells, but not on Th2 cells. Immunofluorescence analyses showed that Th1 cells expressed a higher level of the beta2AR cytoplasmic carboxyl terminus than did Th2 cells. These results show that expression of the beta2AR binding site by Th1 cells, but not by Th2 cells, establishes a physiologic mechanism for selective modulation of Th1 cell IFN-gamma production and IFN-gamma-dependent IgG2a production, provided that beta2AR stimulation occurs before cell activation by a B cell.