Phenomenological studies have established the existence of a neuroimmune axis. This proposal will explore the molecular basis for neuroimmune interactions and seek to delineate the role of the neuromodulator, vasoactive intestinal polypeptide (VIP) in regulation of immune function. VIP is a 28-amino acid peptide found in central and peripheral nervous tissue. We have detected VIP and possibly a pro form of VIP in human blood and bone marrow neutrophils. Experiments are designed to purify this precursor of VIP and to determine its role in immune function. One possible role for VIP in the immune system is modulation of lymphocyte function. A VIP receptor has been detected on lymphocyte plasma membranes. VIP interaction with this receptor activates adenylate cyclase in human peripheral blood lymphocytes and in murine thymocytes. Further experiments will delineate whether the VIP receptor is present on human B lymphocytes, helper or suppressor T lymphocytes, or natural killer cells. The effect of VIP on the function of cloned helper T cells and cytolytic T cells will also be investigated. The molecular basis for VIP modulation of lymphocyte function will then be probed by a study of VIP-mediated activation of cAMP-dependent protein kinase and identification of lymphocyte proteins phosphorylated in the presence of VIP. Finally, the VIP receptor will be purified and characterized, thus allowing production of a monoclonal antibody to this membrane component of human lymphocytes. By these methods, a greater understanding of the nature of the hormone receptor-adenylate cyclase interactions will be defined in human lymphocytes and the physiological role of VIP in the immune response more clearly delineated with clinical relevance to the development of immunotherapeutic regimens for the treatment of infections and neoplasia. (HF)
