title: Pancreas and kidney allograft-infiltrating cells in simultaneous pancreas-kidney transplantation.
abstract: BACKGROUND
  Rejection after pancreas-kidney transplantation may occur isolated or concurrently in both grafts. To get more insight into the cellular mechanisms underlying these rejection episodes, we compared the functional characteristics of pancreas and kidney graft-infiltrating T cells.
  
  
  METHODS
  Graft-infiltrating T cell (GIC) lines were cultured from simultaneously taken pancreas and kidney biopsies from eight patients. CD4 to CD8 ratios were determined by fluorescence-activated cell sorter and cytotoxicity toward donor proximal tubular epithelial cells (PTEC) and donor spleen cells (DSC) using a standard cytotoxicity assay. Cytokine production was determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  CD4 to CD8 ratios were comparable between the pancreas and kidney lines for each patient, but differences were observed in cytotoxicity toward PTEC and DSC. For four of eight patients, the lysis of PTEC by pancreas GIC was less than the lysis induced by kidney GIC. This was also seen in three of five patients for lysis of DSC. The specificity of GIC lines toward mismatched donor antigens was studied for two patients and appeared to be comparable for pancreas and kidney. Most GIC lines produced interferon (IFN)-gamma (75.5+/-22.7 pg/ml), but no IL-10, indicating that the cell lines consisted primarily of Th1 and type 1 CD8+ cells. Mean production of IL-6 was 465.6+/-193.6 pg/ml. No major differences were observed between kidney and pancreas GIC for either cytokine.
  
  
  CONCLUSIONS
  We conclude that pancreas and kidney GIC lines have the same phenotype, cytokine production, and allospecificity. Differences were, however, seen for lysis of PTEC and DSC, suggesting that tissue-specific antigens might play a role.
authors.affiliation: Department of Nephrology, Leiden University Hospital, the Netherlands.
authors.forename: J G
authors.initials: JG
authors.lastname: Boonstra
authors.forename: J G
authors.initials: JG
authors.lastname: Deckers
authors.forename: J C
authors.initials: JC
authors.lastname: Laterveer
authors.forename: V
authors.initials: V
authors.lastname: Price
authors.forename: L A
authors.initials: LA
authors.lastname: van Es
authors.forename: J A
authors.initials: JA
authors.lastname: Bruijn
authors.forename: M R
authors.initials: MR
authors.lastname: Daha
authors.forename: F J
authors.initials: FJ
authors.lastname: van der Woude
mesh_terms: D001706:Biopsy; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D004727:Endothelium / Q000166:cytology; D000939:Epitopes; D006084:Graft Rejection / Q000209:etiology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000166:cytology; D008214:Lymphocytes / Q000166:cytology; D010179:Pancreas / Q000166:cytology* / Q000276:immunology / Q000473:pathology; D016035:Pancreas Transplantation / Q000276:immunology* / Q000473:pathology*; D010641:Phenotype; D013154:Spleen / Q000166:cytology; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000473:pathology
chemical_list: D016207:Cytokines; D000939:Epitopes; D006680:HLA Antigens