title: The Role of T Cell Costimulation via DNAM-1 in Kidney Transplantation.
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.
authors: Institute of Physiology, University of Zurich, Zurich, Switzerland.|Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors: Anna K
authors: AK
authors: Kraus
authors: Institute of Physiology, University of Zurich, Zurich, Switzerland.|Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors: Jin
authors: J
authors: Chen
authors: Institute of Physiology, University of Zurich, Zurich, Switzerland.|Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors: Ilka
authors: I
authors: Edenhofer
authors: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors: Inga
authors: I
authors: Ravens
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland.
authors: Ariana
authors: A
authors: Gaspert
authors: Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors: Pietro E
authors: PE
authors: Cippà
authors: Department of Molecular Genetics and Microbiology, Stony Brook University, New York, New York, United States of America.
authors: Steffen
authors: S
authors: Mueller
authors: Institute of Physiology, University of Zurich, Zurich, Switzerland.|Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors: Rudolf P
authors: RP
authors: Wuthrich
authors: Institute of Physiology, University of Zurich, Zurich, Switzerland.|Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors: Stephan
authors: S
authors: Segerer
authors: Institute of Immunology, Hannover Medical School, Hannover, Germany.
authors: Guenter
authors: G
authors: Bernhardt
authors: Institute of Physiology, University of Zurich, Zurich, Switzerland.|Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
authors: Thomas
authors: T
authors: Fehr
mesh_terms: D064591:Allografts; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics / Q000378:metabolism; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016038:Skin Transplantation; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D053646:Interleukin-2 Receptor beta Subunit; D008024:Ligands; D011991:Receptors, Virus; C066100:poliovirus receptor