Non-hematopoietic allograft cells directly activate CD8+ T cells and trigger acute rejection: an alternative mechanism of allorecognition.
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.
Kreisel
Daniel
D
Department of Surgery, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA.
Krupnick
Alexander S
AS
Gelman
Andrew E
AE
Engels
Friederike H
FH
Popma
Sicco H
SH
Krasinskas
Alyssa M
AM
Balsara
Keki R
KR
Szeto
Wilson Y
WY
Turka
Laurence A
LA
Rosengard
Bruce R
BR
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
D006649:Histocompatibility Antigens; D007376:Interleukin-2; D007519:Isoantigens; D015847:Interleukin-4; D007371:Interferon-gamma