title: Transforming growth factor beta expression by human vascular cells inhibits interferon gamma production and arterial media injury by alloreactive memory T cells.
abstract: Arteriosclerosis is characterized by the local activation of effector T cells leading to production of proinflammatory cytokines, such as IFN (interferon)-γ and IL-17, within the vessel wall. Conversely, the production of antiinflammatory cytokines, for example, TGF-β, by regulatory lymphocytes is known to inhibit both the differentiation of naïve T cells into effector T cells and the development of arteriosclerosis in murine models. We investigated the role of TGF-β on the alloreactivity of human effector memory T cells (Tem). Quiescent vascular cells, but not Tem, expressed TGF-β. Blockade of TGF-β activity in cocultures of CD4(+)  Tem with allogeneic endothelial cells significantly increased IFN-γ, but not IL-17, secretion. Additionally, serologic neutralization of TGF-β in immunodeficient mouse hosts of human coronary artery grafts into which allogeneic human T cells were adoptively transferred resulted in heavier medial infiltration by Tem, greater loss of medial smooth muscle cells and increased IFN-γ production within the grafts without significantly reducing either intimal injury or IL-17 production. Protective effects of TGF-β may be limited by fewer TGF-β-expressing vascular cells within the intimal compartment, by a reduction in the expression of TGF-β by vascular cells in rejecting grafts, or possibly to less effective suppression of Tem than naïve T cells.
authors.affiliation: Department of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Lebastchi
authors.forename: S F
authors.initials: SF
authors.lastname: Khan
authors.forename: L
authors.initials: L
authors.lastname: Qin
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: N
authors.initials: N
authors.lastname: Hibino
authors.forename: T
authors.initials: T
authors.lastname: Yi
authors.forename: D A
authors.initials: DA
authors.lastname: Rao
authors.forename: J S
authors.initials: JS
authors.lastname: Pober
authors.forename: G
authors.initials: G
authors.lastname: Tellides
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D016212:Transforming Growth Factor beta; D007371:Interferon-gamma