title: Murine vascular endothelium activates and induces the generation of allogeneic CD4+25+Foxp3+ regulatory T cells.
abstract: Unlike graft-resident donor-derived hemopoietic APCs, which decrease in number over time after transplantation, vascular endothelial cells are lifelong residents of a vascularized allograft. Endothelial cells are potent APCs for allogeneic CD8+ T lymphocytes but are unable to induce proliferation of allogeneic CD4+ T lymphocytes. Although the reason for this differential response has been poorly understood, here we report that alloantigen presentation by vascular endothelium to CD4+ T lymphocytes activates and induces CD4+25+Foxp3+ regulatory T cells, which can inhibit proliferation of alloreactive T cells both in vitro and in vivo. This process occurs independently of B7.1 costimulation but is dependent on programmed death ligand 1 (B7-H1). This finding may have important implications for tolerance induction in transplantation.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Alexander Sasha
authors.initials: AS
authors.lastname: Krupnick
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Gelman
authors.forename: Winfried
authors.initials: W
authors.lastname: Barchet
authors.forename: Steve
authors.initials: S
authors.lastname: Richardson
authors.forename: Friederike H
authors.initials: FH
authors.lastname: Kreisel
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: G Alexander
authors.initials: GA
authors.lastname: Patterson
authors.forename: Daniel
authors.initials: D
authors.lastname: Kreisel
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014184:Transplantation, Homologous
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2