Non-hematopoietic allograft cells directly activate CD8+ T cells and trigger acute rejection: An alternative mechanism of allorecognition

Daniel Kreisel, Alexander S. Krupnick, Andrew E. Gelman, Friederike H. Engels, Sicco H. Popma, Alyssa M. Krasinskas, Keki R. Balsara, Wilson Y. Szeto, Laurence A. Turka, Bruce R. Rosengard

Research output: Contribution to journalArticlepeer-review

185 Scopus citations

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 antigenpresenting 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.

Original languageEnglish
Pages (from-to)233-239
Number of pages7
JournalNature medicine
Volume8
Issue number3
DOIs
StatePublished - 2002

Fingerprint

Dive into the research topics of 'Non-hematopoietic allograft cells directly activate CD8+ T cells and trigger acute rejection: An alternative mechanism of allorecognition'. Together they form a unique fingerprint.

Cite this