1. Non-hematopoietic allograft cells directly activate CD8+ T cells and trigger acute rejection: An alternative mechanism of allorecognition.
- Author
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Kreisel, Daniel, Krupnick, Alexander S., Gelman, Andrew E., Engels, Friederike H., Popma, Sicco H., Krasinskas, Alyssa M., Balsara, Keki R., Szeto, Wilson Y., Turka, Laurence A., and Rosengard, Bruce R.
- Subjects
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HEMATOPOIESIS , *T cells , *LABORATORY mice - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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