DEVELOPMENT OF IMMUNE HYPERINNERVATION IN NGF-TRANSGENIC MICE

Sympathetic innervation of lymphoid tissues is localized to specific t issue compartments, but little is known of the ''factors'' that are im portant in establishing this pattern during development. Numerous stud ies have shown interactions of nerve growth factor (NGF) with the immu ne system, which may include modulation of immune innervation. We prev iously have shown that NGF transgenic mice, which overexpress NGF in s kin and not immune tissues, have a dramatic hyperinnervation of spleni c marginal zone and peripheral lymph node medulla and capsule. The pur pose of the current studies was to determine if the presence of elevat ed NGF would alter immune system development and the process of sympat hetic ingrowth. The results show that the splenic innervation in NGF t ransgenics gradually diverged from controls during the first two postn atal weeks, with the greatest change occurring between postnatal days 13 and 16 when the splenic organization was reaching the adult pattern . In contrast, the peripheral lymph nodes were hyperinnervated at an e arlier age. Mesenteric lymph nodes never diverged from the normal patt ern. NGF levels in transgenic spleen were much higher than controls at postnatal days 1 and 2, when little innervation was present, and decl ined as the tissue matured, possibly because of NGF uptake by the ingr owing sympathetic fibers. This suggests that immune tissues are capabl e of concentrating NGF, which in turn may modulate the level of innerv ation by the sympathetic nervous system. (C) 1998 Academic Press.