The Role of T Cell Costimulation via DNAM-1 in Kidney Transplantation |
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Authors: | Anna K. Kraus Jin Chen Ilka Edenhofer Inga Ravens Ariana Gaspert Pietro E. Cippà Steffen Mueller Rudolf P. Wuthrich Stephan Segerer Guenter Bernhardt Thomas Fehr |
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Affiliation: | 1. Institute of Physiology, University of Zurich, Zurich, Switzerland;2. Division of Nephrology, University Hospital Zurich, Zurich, Switzerland;3. Institute of Immunology, Hannover Medical School, Hannover, Germany;4. Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland;5. Department of Molecular Genetics and Microbiology, Stony Brook University, New York, New York, United States of America;University of Lisbon, PORTUGAL |
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Abstract: | DNAX accessory protein-1 (DNAM-1, CD226) is a co-stimulatory and adhesion molecule expressed mainly by natural killer cells and T cells. DNAM-1 and its two ligands CD112 and CD155 are important in graft-versus-host disease, but their role in solid organ transplantation is largely unknown. We investigated the relevance of this pathway in a mouse kidney transplantation model. CD112 and CD155 are constitutively expressed on renal tubular cells and strongly upregulated in acutely rejected renal allografts. In vitro DNAM-1 blockade during allogeneic priming reduced the allospecific T cell response but not the allospecific cytotoxicity against renal tubular epithelial cells. Accordingly, absence of DNAM-1 in recipient mice or absence of CD112 or CD155 in the kidney allograft did not significantly influence renal function and severity of rejection after transplantation, but led to a higher incidence of infarcts in CD112 and CD155 deficient kidney allografts. Thus, DNAM-1 blockade is not effective in preventing transplant rejection. Despite of being highly expressed, CD112 and CD155 do not appear to play a major immunogenic role in kidney transplantation. Considering the high incidence of renal infarcts in CD112 and CD155 deficient grafts, blocking these molecules might be detrimental. |
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