title: Non-hematopoietic allograft cells directly activate CD8+ T cells and trigger acute rejection: an alternative mechanism of allorecognition.
abstract: Despite evidence that human non-hematopoietic cells, such as vascular endothelium, can activate allogeneic T lymphocytes in vitro, the prevailing view has been that hematopoietic antigen-presenting cells are required to trigger alloimmune responses in vivo. Here we report that mouse non-hematopoietic cells activate alloreactive CD8+ T lymphocytes in vitro and in vivo. We also show that vascularized cardiac allografts are acutely rejected via CD8+ direct allorecognition even if the alloantigen is not presented by hematopoietic professional antigen-presenting cells. Because activation of alloreactive CD8+ T cells by donor-type non-hematopoietic cells can continue for the life of the allograft, these findings present a new clinically relevant mechanism of allorecognition and should be taken into consideration when developing strategies to prevent allograft vasculopathy or to induce tolerance.
authors.affiliation: Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kreisel
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Krupnick
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Gelman
authors.forename: Friederike H
authors.initials: FH
authors.lastname: Engels
authors.forename: Sicco H
authors.initials: SH
authors.lastname: Popma
authors.forename: Alyssa M
authors.initials: AM
authors.lastname: Krasinskas
authors.forename: Keki R
authors.initials: KR
authors.lastname: Balsara
authors.forename: Wilson Y
authors.initials: WY
authors.lastname: Szeto
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Rosengard
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D006084:Graft Rejection / Q000276:immunology* / Q000503:physiopathology; D016027:Heart Transplantation / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology* / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009206:Myocardium / Q000473:pathology; D013154:Spleen / Q000166:cytology; D018183:Transplantation Chimera; D014184:Transplantation, Homologous / Q000276:immunology* / Q000502:physiology
chemical_list: D006649:Histocompatibility Antigens; D007376:Interleukin-2; D007519:Isoantigens; D015847:Interleukin-4; D007371:Interferon-gamma