NGF MODULATES SYMPATHETIC INNERVATION OF LYMPHOID-TISSUES

Immune tissues are known to be innervated by the sympathetic nervous s ystem, but little is known of what directs the innervation to specific tissue compartments. This report examines the sympathetic innervation of immune tissues in transgenic mice that overexpress nerve growth fa ctor (NGF) in skin and other epithelial structures. NGF transgenic mic e exhibited dramatic hyperinnervation in the splenic marginal zone, an d the medulla and capsule of peripheral lymph nodes. In contrast, the transgenic mesenteric lymph nodes showed no hyperinnervation. This dif ference correlated with the location of these nodes; peripheral lymph nodes drain skin where the transgene was expressed while mesenteric ly mph nodes drain non-transgene-expressing structures. In addition, the level of innervation correlated with the level of NGF peptide content as assayed by ELISA (3- and 13-fold increase in transgenic spleen and axillary lymph nodes, respectively; no increase in mesenteric nodes) a nd immunocytochemistry. RT-PCR showed that the NGF transgene was not b eing expressed in the immune tissues, suggesting that immune tissues c an concentrate transgene-produced NGF. It was also demonstrated that t he change in innervation had functional consequences. The mitogen resp onse to concanavalin A (ConA) by spleen cells was decreased in the tra nsgenics suggesting that elevated catecholamines or NGF can modulate t he proliferative response of these cells. These mice demonstrate that NGF can modulate the sympathetic innervation and function of the immun e system.