title: Costimulation of human CD4+ T cells by fibroblast growth factor-1 (acidic fibroblast growth factor).
abstract: T cell infiltration is prevalent in wound healing, atherosclerosis, vascular lesions in chronic allograft rejection, and autoimmune diseases. Whether T cells play a role in the migration and proliferation of vascular smooth muscle cells and endothelial cells in these lesions is not known. We previously reported that some human T cells express FGF-1, a potent growth factor for vascular smooth muscle cells and endothelial cells. In this study, we extend this observation and examine the expression and function of FGF receptors on human T cells. Using reverse transcription-PCR, Northern analysis, and immunohistochemistry, we found that some human T cells also express high affinity FGF receptor 1 (FGFR-1) respond to FGF-1. In the presence of anti-CD3, exogenous FGF-1 functions as a costimulator for these T cells, while FGF-1 alone does not induce T cell proliferation. [3H]Thymidine incorporation is sevenfold higher in T cells costimulated with FGF-1 compared with stimulation with anti-CD3 alone. Using limiting dilution, we demonstrate that FGF-responsive T cells are present in normal peripheral blood at a mean frequency of 1:19780 (95% confidence limits, 1:15100-1:23000), and similar T cells are increased in the peripheral blood of heart transplant recipients (mean frequency, 1:4210; 95% confidence limits, 1:3420-1:6781). In addition, a subline of Jurkat, a human T cell tumor, expresses FGFR-1 receptor. The function of FGFR-1 receptor in Jurkat T cells is demonstrated by the production of IL-2 after stimulation with FGF-1 and anti-CD3. IL-2 levels are sevenfold higher in Jurkat T cells costimulated with FGF-1 compared with those stimulated with anti-CD3 alone. FGF-1 alone has no effect on Jurkat T cells. These findings thus provide evidence that a subset of human T cells expresses a receptor for vascular cell growth factors, and this receptor functions to increase IL-2 production consistent with costimulation. The potential role of FGF-responsive T cells in a variety of vascular and inflammatory lesions is discussed.
authors.affiliation: Vanderbilt Transplant Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: X M
authors.initials: XM
authors.lastname: Zhao
authors.forename: V M
authors.initials: VM
authors.lastname: Byrd
authors.forename: W L
authors.initials: WL
authors.lastname: McKeehan
authors.forename: M B
authors.initials: MB
authors.lastname: Reich
authors.forename: G G
authors.initials: GG
authors.lastname: Miller
authors.forename: J W
authors.initials: JW
authors.lastname: Thomas
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D002999:Clone Cells; D016220:Fibroblast Growth Factor 1 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D018655:Lymphocyte Count; D012333:RNA, Messenger / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics; D013234:Stem Cells / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016220:Fibroblast Growth Factor 1