TY - JOUR

T1 - Cytotoxic T lymphocytes and natural killer cells display impaired cytotoxic functions and reduced activation in patients with alcoholic hepatitis

AU - Støy, Sidsel

AU - Dige, Anders

AU - Sandahl, Thomas Damgaard

AU - Laursen, Tea Lund

AU - Buus, Christian

AU - Hokland, Marianne

AU - Vilstrup, Hendrik

N1 - Copyright © 2014, American Journal of Physiology- Gastrointestinal and Liver Physiology.

PY - 2014/12/11

Y1 - 2014/12/11

N2 - Background & aims: The dynamics and role of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells and NKT cells in the life-threatening inflammatory disease alcoholic hepatitis is largely unknown. These cells directly kill infected and damaged cells through e.g. degranulation and IFNγ production, but cause tissue damage if over-activated. They also assist tissue repair via IL-22-production. We, therefore, aimed to investigate the frequency, functionality and activation state of such cells in alcoholic hepatitis. Methods: We analysed blood samples from 24 severe alcoholic hepatitis patients followed for 30 days after diagnosis. Ten healthy abstinent volunteers and 10 stable abstinent alcoholic cirrhosis patients were controls. Using flow cytometry we assessed cell frequencies, NK cell degranulation capacity following K562 cell stimulation, activation by NKG2D expression, and IL-22 and IFNγ production. Results: In alcoholic hepatitis we found a decreased frequency of CTLs compared with healthy controls (p<0.001) and a similar trend for NK cells (p=0.089). The NK cell degranulation capacity was reduced by 25% compared with healthy controls (p=0.02) and by 50% compared with cirrhosis patients (p=0.04). Accordingly the NKG2D receptor expression was markedly decreased on NK-, CTLs and NKT cells (p<0.05, all). The frequencies of IL-22-producing CTLs and NK cells were doubled compared with healthy controls (p<0.05, all) but not different from cirrhosis patients. Conclusions: This exploratory study for the first time showed impaired cellular cytotoxicity and activation in alcoholic hepatitis. This is unlikely to cause hepatocyte death but may contribute towards the severe immune incompetence. The results warrant detailed and mechanistic studies.

AB - Background & aims: The dynamics and role of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells and NKT cells in the life-threatening inflammatory disease alcoholic hepatitis is largely unknown. These cells directly kill infected and damaged cells through e.g. degranulation and IFNγ production, but cause tissue damage if over-activated. They also assist tissue repair via IL-22-production. We, therefore, aimed to investigate the frequency, functionality and activation state of such cells in alcoholic hepatitis. Methods: We analysed blood samples from 24 severe alcoholic hepatitis patients followed for 30 days after diagnosis. Ten healthy abstinent volunteers and 10 stable abstinent alcoholic cirrhosis patients were controls. Using flow cytometry we assessed cell frequencies, NK cell degranulation capacity following K562 cell stimulation, activation by NKG2D expression, and IL-22 and IFNγ production. Results: In alcoholic hepatitis we found a decreased frequency of CTLs compared with healthy controls (p<0.001) and a similar trend for NK cells (p=0.089). The NK cell degranulation capacity was reduced by 25% compared with healthy controls (p=0.02) and by 50% compared with cirrhosis patients (p=0.04). Accordingly the NKG2D receptor expression was markedly decreased on NK-, CTLs and NKT cells (p<0.05, all). The frequencies of IL-22-producing CTLs and NK cells were doubled compared with healthy controls (p<0.05, all) but not different from cirrhosis patients. Conclusions: This exploratory study for the first time showed impaired cellular cytotoxicity and activation in alcoholic hepatitis. This is unlikely to cause hepatocyte death but may contribute towards the severe immune incompetence. The results warrant detailed and mechanistic studies.

U2 - 10.1152/ajpgi.00200.2014

DO - 10.1152/ajpgi.00200.2014

M3 - Journal article

C2 - 25501547

SP - ajpgi.00200.2014

JO - A J P: Gastrointestinal and Liver Physiology (Online)

JF - A J P: Gastrointestinal and Liver Physiology (Online)

SN - 1522-1547

ER -