title: Platelet-derived growth factor is a potent biologic response modifier of T cells.
abstract: Freshly isolated lymph node (LN) cells cultured in serum-containing medium were restricted to produce primarily interleukin 2 (IL-2) subsequent to T cell activation. Only minimal amounts of IL-4, IL-5, or interferon gamma (IFN-gamma) were produced under these conditions. Similar populations of LN cells cultured in serum-free medium were able to produce a variety of lymphokines after T cell activation, with the relative quantities of each species being dependent upon the lymphoid organ source of the lymphocytes. A similar relationship in the patterns of lymphokines produced by activated T cell hybridomas maintained under serum-free conditions was also observed, whereas activation in serum-supplemented media resulted in a predominant restriction to the secretion of IL-2. Additional studies determined that the entity in serum responsible for restricting T cell function in vitro was platelet-derived growth factor (PDGF). The PDGF-BB isoform was established to be the most active in the regulation of T cell function, enhancing IL-2 while depressing the production of IL-4, IL-5, and IFN-gamma at concentrations below 1 ng/ml. PDGF-AB was also found to be quite active, however, this isoform of PDGF was incapable of influencing IFN-gamma production at the concentrations tested. PDGF-AA was very weakly active. It therefore appears that PDGF, acting primarily through a beta receptor subunit (either alpha/beta- or beta/beta-type receptors) is able to influence profoundly the behavior of T cells, with some of its modulatory effects exhibiting isoform specificity. This is reflected by an enhancement in the production of IL-2, while simultaneously depressing the secretion of IL-4, IL-5, and IFN-gamma (PDGF-BB only) after T cell activation. Kinetic studies, where cell supernatants were analyzed both 24 and 48 h after T cell activation, suggested that "desensitization" to PDGF influences can occur naturally in vitro. Those species of lymphokines that were inhibited by PDGF over the first 24 h after activation could be produced at normal levels over the subsequent 24-h period. Finally, lymphokines maintained in the presence of PDGF-BB for greater than 24 h before their activation lost sensitivity to this growth factor. These cells regained responsiveness to PDGF after an additional incubation period in PDGF-free medium. Collectively, our data imply that the pattern of T cell lymphokines produced, plus the kinetics of their production after activation, are being controlled by the potent serum growth factor PDGF.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Division of Cell Biology and Immunology, University of Utah School of Medicine, Salt Lake City 84132.
authors.forename: R A
authors.initials: RA
authors.lastname: Daynes
authors.forename: T
authors.initials: T
authors.lastname: Dowell
authors.forename: B A
authors.initials: BA
authors.lastname: Araneo
mesh_terms: D000818:Animals; D001790:Blood Physiological Phenomena; D002478:Cells, Cultured; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology; D017479:Receptors, Platelet-Derived Growth Factor; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D007155:Immunologic Factors; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017479:Receptors, Platelet-Derived Growth Factor