9. Thymic hormone stimulation of pituitary hormone release

87 stimulus secretion coupling mechanism does not involve polyphosphoinositide hydrolysis or cAMP generation, but appears to be dependent upon the generation of arachidonate metabolites. 10. Innervation of lymphoid tissue - - Suzanne Y. Felten and David L. Felten (University of Rochester School of Medicine, Department of Anatomy, Rochester, NY 14642, U.S.A) Direct neuronal connections between the central nervous system and various primary and secondary lymphoid tissues have been demonstrated using a number of anatomical techniques used separately and in combination, including histochemistry, histofluorescence, immunocytochemistry, electron microscopy, immunoelectron microscopy, and pathway tracing. Studies of this nature have provided clear and unequivocal evidence that sympathetic postganglionic autonomic nerve fibers innervate thymus, spleen, and lymph nodes. These nerve fibers arise from sympathetic chain ganglion such as the superior cervical (thymus) or from collateral ganglia such as the coeliac-superior mesenteric (spleen), which, in turn receive input from the intermediolateral cells column of the thoracohimbar spinal cord. The intermediolateral cells column, in turn, receives projections from central autonomic sites such as the paraventricular nucleus of the hypothalamus, and the dorsal vagal complex. The noradrenergic sympathetic innervation enters the organ in association with blood vessels, but branches from these vessels to innervate the lymphatic parenchyma as well. It is most often closely associated with zones of lymphoid tissue containing T lymphocytes, including both the cortex and corticomedullary boundary of the thymus, the white pulp of the spleen, and the non-nodular regions of the lymph node. In the spleen, where the innervation has been investigated in great detail, the noradrenergic nerve fibers are specifically associated with the periarteriolar lymphatic sheath, the inner marginal zone, and the parafollicular zone in addition to innervation of the capsule, trabeculae and vasculature. Studies at the EM level confirm that noradrenergic fibers are in direct contact with lymphocytes. In the lymph node, capsular, paracortical zones, and medullary areas, particularly near the hilus are also innervated. The clear existence of a neuronal pathway by which the CNS might influence cells of the immune system provides a much needed additional link between psychosocial factors impacting on an individual and the outcome of disease. (Supported by N00014-84-K-0488 from the Office of Naval Research) 11. Nonadrenergic neurotransmission in the spleen - - David L. Felten and Suzanne Y. Felten (Department of anatomy, University of Rochester School of Medicine, Rochester, NY 14642, U.S.A.) The noradrenergic innervation supplying the spleen fulfills the major criteria for neurotransmission, with lymphoid cells as the target tissue. Anatomically, noradrenergic fibers derived from coeliac-superior mesenteric ganglion cells, enter the spleen with the vasculature, and distribute into specific compartments of the white pulp. Double labelled immunocytochemistry has shown tyrosine hydroxylase-positive fibers adjacent to T lymphocytes in the periarteriolar lymphatic sheath, and adjacent to ED-3-positive macrophages at the marginal sinus. The spleen contains a high concentration of NE and its metabolites, a content that can be depleted by 6-hydroxydopamine, suggesting that it is found in the neural compartment. In vivo dialysis measurements of NE available in the extracellular space demonstrates the availability of a high concentration, in the range of 1 /~M, of NE, apparently derived from release. In addition lymphocytes possess beta-adrenergic receptors linked with cyclic AMP as a second messenger, and are able to alter intracellular metabolic events upon stimulation. At a functional level, in adult mice denervated with 6-hydroxydopamine, primary and secondary antibody responses are markedly diminished in spleen and lymph nodes, suggesting that these nerves are important for full immunocompetence. In the aged Fischer 344 rat, the splenic noradrenergic innervation is reduced in all compartments, particularly in the parenchymal compartment, and the content of NE is reduced. The possibility of a causal relationship between diminished sympathetic noradrenergic innervation and diminished immune responsiveness in these aged rodents is currently being explored. We also have challenged lymphocytes in order to observe the potential plasticity for the NE fibers innervating the white pulp. If lymphocytes are destroyed with hydrocortisone or cyclophosphamide, the splenic weight diminishes and the white pulp shrinks, but the splenic NE content remains constant; however, the fiber density increases in the white pulp as the fibers retract to maintain their original compartmentation, indicating that replenishing lymphocyte populations will encounter higher concentrations of NE than in control spleens. If lympho-