title: Liver grafts from CD39-overexpressing rodents are protected from ischemia reperfusion injury due to reduced numbers of resident CD4+ T cells.
abstract: Ischemia-reperfusion injury (IRI) is a major limiting event for successful liver transplantation, and CD4+ T cells and invariant natural killer T (iNKT) cells have been implicated in promoting IRI. We hypothesized that hepatic overexpression of CD39, an ectonucleotidase with antiinflammatory functions, will protect liver grafts after prolonged cold ischemia. CD39-transgenic (CD39tg) and wildtype (WT) mouse livers were transplanted into WT recipients after 18 hours cold storage and pathological analysis was performed 6 hours after transplantation. Serum levels of alanine aminotransferase and interleukin (IL)-6 were significantly reduced in recipients of CD39tg livers compared to recipients of WT livers. Furthermore, less severe histopathological injury was demonstrated in the CD39tg grafts. Immune analysis revealed that CD4+ T cells and iNKT cells were significantly decreased in number in the livers of untreated CD39tg mice. This was associated with a peripheral CD4+ T cell lymphopenia due to defective thymocyte maturation. To assess the relative importance of liver-resident CD4+ T cells and iNKT cells in mediating liver injury following extended cold preservation and transplantation, WT mice depleted of CD4+ T cells or mice genetically deficient in iNKT cells were used as donors. The absence of CD4+ T cells, but not iNKT cells, protected liver grafts from early IRI.
  
  
  CONCLUSIONS
  Hepatic CD4+ T cells, but not iNKT cells, play a critical role in early IRI following extended cold preservation in a liver transplant model.
authors: Immunology Research Centre, St Vincent's Hospital, Melbourne, Australia.
authors: Sandra
authors: S
authors: Pommey
authors: Bo
authors: B
authors: Lu
authors: Jennifer
authors: J
authors: McRae
authors: John
authors: J
authors: Stagg
authors: Prue
authors: P
authors: Hill
authors: Evelyn
authors: E
authors: Salvaris
authors: Simon C
authors: SC
authors: Robson
authors: Anthony J F
authors: AJ
authors: d'Apice
authors: Peter J
authors: PJ
authors: Cowan
authors: Karen M
authors: KM
authors: Dwyer
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001081:Apyrase / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000097:blood; D007694:Killer Cells, Natural / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology / Q000473:pathology*; D008231:Lymphopenia / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D050378:T-Lymphocytes, Regulatory / Q000473:pathology; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D015850:Interleukin-6; D000410:Alanine Transaminase; D001081:Apyrase; C067869:CD39 antigen