title: Substance P increases and prolongs increased output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo: is it a mediator of immunological memory?
abstract: There are receptors on lymphocytes for substance P which are found both on small recirculating and on blast lymphocytes. The principal effect of substance P on lymphocytes appears to be a stimulating one, both in vitro and in vivo. The in vivo administration of substance P to sheep by acute infusion into cannulated afferent lymphatics of peripheral lymph nodes has been found to stimulate efferent lymph flow and the output into efferent lymph of both small recirculating and blast lymphocytes. We here report that substance P both enhances and prolongs the enhancement of the output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo. This output-stimulating effect appears to be specific to T4 (CD4) lymphocytes and is associated with a depressant effect on the output of T8 (CD8) and B lymphocytes. The output-stimulating effect on small T4 (CD4) lymphocytes is quite prolonged, lasting in excess of 96 h after a single 50 micrograms acute infusion. A brief post-infusion depression in T4 (CD4) lymphocyte output is associated with an equally brief, but marked, elevation in the output into efferent lymph of the arachidonic acid metabolite, thromboxane B2. The output-stimulating effect of substance P on blast T lymphocytes is confined to the T4 (CD4) blast lymphocytes. Substance P or a similar molecule may be of value when a specific T4 (CD4) lymphocyte output stimulant effect is desired. A single prior (6 days) acute infusion of substance P into a popliteal lymph node via its cannulated afferent lymphatic produced profound changes in the response to nodal drainage area immunization with killed S. muenchen bacteria. The latent period prior to increased antibody production was abolished, as was the standard post-immunization 'shutdown' period of decreased output of lymphocytes into efferent lymph. These changes were accompanied by a marked and progressive increase in antibody production. The findings reported here suggest substance P-induced long-term potentiation (LTP) of the immune response and raise the question of an involvement of substance P as a major mediator of immunological memory.
authors.affiliation: Department of Surgery, UCLA School of Medicine.
authors.forename: T C
authors.initials: TC
authors.lastname: Moore
authors.forename: G A
authors.initials: GA
authors.lastname: Whitley
authors.forename: J L
authors.initials: JL
authors.lastname: Lami
authors.forename: S I
authors.initials: SI
authors.lastname: Said
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D007156:Immunologic Memory / Q000187:drug effects* / Q000502:physiology; D008208:Lymphatic System / Q000166:cytology / Q000187:drug effects; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D012756:Sheep; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology
chemical_list: D013373:Substance P