Neuroimmunology THE production of neuropeptide Y (NPY) in lymphocytes obtained from human tonsils was investigated using radioimmunoassay. White unstimulated lymphocytes did not produce detectable amounts of NPY, NPY synthesis was induced after cell activation. Our results show that the addition of nerve growth factor (NGF) to unstimu- lated lymphocytes has an effect similar to that of mitogens, both leading to productian of NPY. The study of purified B and T cells confirmed that only activated cells are able to synthesize NPY. The stimula- - tory effect of NGF on NPY productian is not a common characteristic of all lymphocytes: only unstimulated T ceUs respond to NGF by synthesizing NPY. No such cffects is seen in purified B cells. Key Words: NGF; NPY production; lymphocytes; T cells; Neuroimmunomodulation lntroduction Nerve growth factor (NGF), in addition to its neurotrophic actions, has broader physiological effects than the regulation of neuronal function. 1 Numerous in vitra studies have demonstrated that NGF can affect the survival, differentiation and proliferation of lymphocytes/• 3 granulocytes 4 and mast cells. 5 The biological effects of NGF are directly dependent on initial binding of NGF to specific cell surface receptors. Low affinity NGF receptors have been found in rat splenocytes 6 and mast cells/ and in human B and T lymphocytes, 2 while only recently trk.A expression was observed in mast cells, 8 mono- cytes,9 murine T cell clones 10 and B cells. 11 Inflammatory stimuli contribute to increase NGF production, and inflammatory cytokines are potent inducers of NGF synthesis, as demonstrated in both in vitra and in viva studies. 12 • 13 Autoimmune diseases that are characterized by abnorma! activation of the immune system and increased productian of cyto- kines are also associated with increased levels of NGF. 14 • 15 These data indicate that NGF can act as an immunamodulator and may play an important role in the camplex network of bidirectional signals between the nervous and immune systems. Neuropeprides represent another group of molecules invalved in the neuronal modulation of the immune function. Neuropeprides released at the nerve fihre endings can bind to their specific receptor present on immune cells and, as indicated by recent studies, modulate the immune response by acting direccly on leukocytes. 16 © Rapid Science Publishars neuro(ieport NeuroReport 7, 485-488 (1996) Nerve growth factor stimulates productian of neuropeptida V in human lymphocytes Luisa Bracci-Laudiero, 1 • 2 Luigi Aloe, 1 ,cA Carina Stenfors, 2 Paola Tirassa, 1 Elvar Theodorsson 3 and Thomas Lundberg 2 1 1nstitute of Neurobiology CNR, Viale C. Marx 15, 00137 Rome, ltaly; 2 Karolinska Institutet, Stockholm; 3 University Hospital, Linkiping, Sweden CACorresponding Author Neuropepride Y, a 36 residue peptide widely distributed in the central and peripheral nervous systems, has been detected in lymphoid organs. 17 • 18 The presence of NPY in the organs of the immune system is due not only to the sympathetic innervation of these organs hut also to a basal productian by immune cells as indicated by studies in vitra and in viva. 19 - 21 The expression of NPY mRNA has recently been detected in human lymphoblasts 22 and lymphocytes, 23 although productian of the protein has not been investigated. The mechanism by which NPY synthesis in the immune system is regulated is not known. Studies on the nervous system show that NGF 24 • 25 can influence NPY expression hut no studies have been carried out to investigate whether the same effect occurs in the immune cells. In the present study we analysed NPY productian by purified human lymphocytes and the effect of different mitogens on its synthesis. We also investi- gated whether exogenous administration of NGF can effect NPY productian in human lymphocytes. Materials and Methods Cell culture: Three human tonsils obtained at routine tonsillectomy were minced in sterile PBS and mechanically dissociated inta a single suspension. After Ficoll-Hypaque (Pharmacia, Uppsala, Sweden) gradient centrifugation and depletion of adherent cells by adhesion to plastic dishes, the lymphocytes were further separated inta T and B cells using the E- Vol 7 No 2 31 January 1996 485