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MELD and Child-Pugh Scores Are Related to Immune Status of Intrahepatic Natural Killer Cells in Liver Transplant Candidates
- Source :
- Transplantation proceedings. 49(1)
- Publication Year :
- 2017
-
Abstract
- Background The role and phenotypic alterations of intrahepatic natural killer (NK) cells in liver disease were investigated. Although intrahepatic NK cells reportedly functionally deteriorate in the fibrotic liver, it remains unclear how the clinical severity of liver disease affects intrahepatic NK cells in patients with advanced liver failure. Methods We analyzed the phenotypic properties of intrahepatic NK cells by using mononuclear cells extracted from ex vivo liver perfusate effluents from patients who underwent liver transplantation. The relationship between the clinical severity of liver disease and the phenotype of intrahepatic NK cells in these patients was also evaluated. To estimate the immunological responsiveness of intrahepatic NK cells, phenotypic enhancement after interleukin-2 stimulation was analyzed. Results Intrahepatic NK cells from patients with advanced liver failure exhibited down-regulated monomodal expression of NKp46, a major activating molecule. Notably, the expression level of NKp46 decreased depending on the severity of liver disease, Model for End-Stage Liver Disease score, and Child-Pugh score rather than the etiology. After in vitro recombinant interleukin-2 stimulation, the enhancement of expression of cytotoxic molecules, NKp44, and tumor necrosis factor–related apoptosis-inducing ligand was significantly impaired in intrahepatic NK cells from patients with liver failure, concurrently with decreased expression of CD122 and interleukin-2 receptor beta. Conclusions Our results suggest that terminal deterioration of liver environments by chronic liver disease impairs the potential of local NK cells, depending on the severity of the deterioration. These influences of advanced liver failure on intrahepatic NK cells may be attributed to multicentric carcinogenesis in patients with liver failure.
- Subjects :
- 0301 basic medicine
Adult
Male
medicine.medical_treatment
Stimulation
Biology
Liver transplantation
Chronic liver disease
Peripheral blood mononuclear cell
Flow cytometry
End Stage Liver Disease
03 medical and health sciences
Liver disease
0302 clinical medicine
medicine
Humans
Receptor
Transplantation
medicine.diagnostic_test
Middle Aged
medicine.disease
Flow Cytometry
Liver Transplantation
Killer Cells, Natural
030104 developmental biology
Immunology
030211 gastroenterology & hepatology
Surgery
Tumor necrosis factor alpha
Female
Subjects
Details
- ISSN :
- 18732623
- Volume :
- 49
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Transplantation proceedings
- Accession number :
- edsair.doi.dedup.....9ffcdac20c6231edf1b212cdf0968304