Activation of antigen-specific CD4+ Th2 cells and B cells in vivo increases norepinephrine release in the spleen and bone marrow
Activation of antigen-specific CD4+ Th2 cells and B cells in vivo increases norepinephrine release in the spleen and bone marrow
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DOI：
10.4049/jimmunol.165.2.725
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发表时间：
2000-07-15
影响因子：
4.4
通讯作者：
Jones, SB
中科院分区：
文献类型：
--
作者：
Kohm, AP;Tang, YM;Jones, SB
神经递质去甲肾上腺素(NE)与多种免疫细胞上表达的β(2)-肾上腺素能受体(β(2)AR)结合，影响细胞归巢、增殖和功能。先前的报道表明，去甲肾上腺素对B细胞β(2)受体的刺激是维持体内最佳的Th2细胞依赖的抗体反应所必需的。在这项研究中，我们研究了体内抗原特异的CD4(+)Th2细胞和B细胞被一种可溶性蛋白Ag激活的机制，它增加了脾和骨髓中NE的释放。我们的模型系统使用的是SCID小鼠，它们是由锁孔帽状血蓝蛋白特异性Th2细胞和三硝基苯特异性B细胞的克隆重组而成的。免疫后，用[H-3]NE周转率分析测定脾和骨髓中NE的释放率。重组SCID小鼠接种同源抗原后18~25h，脾和骨髓NE释放率增加，但1~8h无明显变化。相反，非同源抗原免疫小鼠在任何时候都不影响NE的释放速率。同源Ag诱导的去甲肾上腺素释放增加可被氯异丹明部分阻断，提示节前和节后信号在调节去甲肾上腺素释放中起作用。因此，体内抗原特异的Th2细胞和B细胞被一种可溶性蛋白Ag激活，可增加免疫后18-25h脾和骨髓中NE的释放和周转速度。
The neurotransmitter norepinephrine (NE) binds to the beta(2)-adrenergic receptor (beta(2)AR) expressed on various immune cells to influence cell homing, proliferation, and function. Previous reports showed that NE stimulation of the B cell beta(2)AR is necessary for the maintenance of an optimal primary and secondary Th2 cell-dependent Ab response in vivo. In the present study we investigated the mechanism by which activation of Ag-specific CD4(+) Th2 cells and B cells in vivo by a soluble protein Ag increases NE release in the spleen and bone marrow. Our model system used scid mice that were reconstituted with a clone of keyhole limpet hemocyanin-specific Th2 cells and trinitrophenyl-specific B cells. Following immunization, the rate of NE release in the spleen and bone marrow was determined using [H-3]NE turnover analysis. Immunization of reconstituted scid mice with a cognate Ag increased the rate of NE release in the spleen and bone marrow 18-25 h, but not 1-8 h, following immunization. In contrast, immunization of mice with a noncognate Ag had no effect on the rate of NE release at any time. The cognate Ag-induced increase in NE release was partially blocked by ganglionic blockade with chlorisondamine, suggesting a role for both pre- and postganglionic signals in regulating NE release. Thus, activation of Ag-specific Th2 cells and B cells in vivo by a soluble protein Ag increases the rate of NE release and turnover in the spleen and bone marrow 18-25 h after immunization.