title: Distribution of intrahepatic T, NK and CD3(+)CD56(+)NKT cells alters after liver transplantation: Shift from innate to adaptive immunity?
abstract: BACKGROUND
  The liver is an immunological organ containing a large number of T, NK and NKT cells, but little is known about intrahepatic immunity after LTx. Here, we investigated whether the distribution of T, NK and CD3(+)CD56(+)NKT cells is altered in transplanted livers under different circumstances.
  
  
  METHODS
  Core biopsies of transplanted livers were stained with antibodies against CD3 and CD56. Several cell populations including T (CD3(+)CD56(-)), NK (CD3(-)CD56(+)) and NKT cells (CD3(+)CD56(+)) were studied by fluorescence microscopy. Cell numbers were analyzed in relation to the time interval after LTx, immunosuppressive therapy and stage of acute graft rejection (measured with the rejection activity index: RAI) compared to tumor free liver tissue from patients after liver resection due to metastatic disease as control.
  
  
  RESULTS
  Recruitment of CD3(+)CD56(+)NKT cells revealed a significant decrease during high RAI scores in comparison to low and middle RAI scores (RAI 7-9: 0.03±0.01/HPF vs. RAI 4-6: 0.1±0.005/HPF). CD3(+)CD56(+)NKT cells were also lower during immunosuppressive therapy with tacrolimus (0.03±0.01/HPF) than with cyclosporine (0.1±0.003/HPF), cyclosporine/MMF (0.1±0.003/HPF) or sirolimus (0.1±0.01/HPF) treatment. Intrahepatic T cell numbers increased significantly 50days after LTx compared to control liver tissue (4.5±0.2/HPF vs. 1.9±0.1/HPF). In contrast, NK cells (0.3±0.004/HPF) were significantly fewer in all biopsies after LTx compared to the control (0.7±0.04/HPF).
  
  
  CONCLUSIONS
  These data indicate significant alterations in the hepatic recruitment of T, NK and CD3(+)CD56(+)NKT cells after LTx. The increase in T cells and the decrease in NK and CD3(+)CD56(+)NKT cells suggest a shift from innate to adaptive hepatic immunity in the liver graft.
authors.affiliation: University Hospital Regensburg, Department of Surgery, Regensburg, Germany.
authors.forename: Jens M
authors.initials: JM
authors.lastname: Werner
authors.forename: Corinna
authors.initials: C
authors.lastname: Lang
authors.forename: Marcus N
authors.initials: MN
authors.lastname: Scherer
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Farkas
authors.forename: Edward K
authors.initials: EK
authors.lastname: Geissler
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Schlitt
authors.forename: Matthias
authors.initials: M
authors.lastname: Hornung
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D017252:CD3 Complex; D019002:CD56 Antigen; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000473:pathology; D016559:Tacrolimus; D014184:Transplantation, Homologous
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; D007166:Immunosuppressive Agents; C522918:NCAM1 protein, human; D016559:Tacrolimus