Activation of antigen-specific CD4(+) Th2 cells and B cells in vivo increases norepinephrine release in the spleen and bone marrow

The neurotransmitter norepinephrine (NE) binds to the beta(2)-adrenergic re ceptor (beta(2)AR) expressed on various immune cells to influence cell homi ng, proliferation, and function. Previous reports showed that NE stimulatio n of the B cell beta(2)AR is necessary for the maintenance of an optimal pr imary 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 relea se 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 N E release in the spleen and bone marrow was determined using [H-3]NE turnov er analysis. Immunization of reconstituted scid mice with a cognate Ag incr eased 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 no ncognate Ag had no effect on the rate of NE release at any time. The cognat e Ag-induced increase in NE release was partially blocked by ganglionic blo ckade with chlorisondamine, suggesting a role for both pre- and postganglio nic signals in regulating NE release. Thus, activation of Ag-specific Th2 c ells and B cells in vivo by a soluble protein Ag increases the rate of NE r elease and turnover in the spleen and bone marrow 18-25 h after immunizatio n.