The Research On Functions Of Natural Killer Cells In Chronic HCV Infection And Treatment

Hepatitis c virus (HCV) infection is one of the leading causes in end-stage liver disease.It is estimated that approximately200million individuals infected HCV, after exposured toHCV, about50-90%of asymptomatic patients cannot spontaneously clear virus, andprocessed to chronic HCV infection and caused to chronic hepatitis, cirrhosis and livercancer. Currently researches have shown that the outcome and therapeutic effect of HCVinfection was related to host immunity, virus genetype, liver microenviroment, of whichimmune response in chronic HCV patients was the most important mechanism in thisprocess.Previous research focused on CD8+T cells (CTL), now more researches focus on innateimmune system in prognosis of HCV infection and pathogenesis. NK cells are the majorcomponents of the innate immune system, a few research proved that NK cells in thepathogenesis plays an important role, but the role in therapy with IFN-α combined libavilinis uncertain. IFN-α has been shown to potential stimulating factor of NK cells, how NK cellsactivated in the treatment and how to play a immunological role on antiviral activity is stillnot clear.Study on phenotypes and functions of NK cells before and after IFN-α treatment:⑴35chronic HCV patient is recruitd, treated with standard interferon (n=22) andpegylated interferon (n=13) respectively.⑵Frequency,phaenotype and functions of NK cells in chronic HCV patients weredetected by flow cytometry at baseline,4week,12week,24week,48week and72week。Results are as follows:⑴In chronic HCV patients, NK cells, CD3-CD56^birghtNK, CD3-CD56dimNK cell wereno significant difference, while CD56^birghtNK was correlated with ALT.⑵In chronic HCV patients, activating receptors NKG2C, NKG2D, NKp46, inhibitoryreceptor CD158a and CD158b were significant increasing, NKG2C were positivelycorrelated with ALT, CD158a are negatively correlated with ALT.⑶In chronic HCV patients, TRAIL and CD107a on NK cell were no significantlydifference, CD107a were positively correlated with ALT. IFN-γ secretion was decreased. ⑷After treatment, CD56brightNK cells in chronic HCV infection were significantlyincreased. Activating receptor NKG2C was decreased, NKp30and NKp46was increased;inhibitory receptor CD158a and CD158b were decreased. The therapy-induced decrease inHCV-RNA strongly correlated with the therapy-induced change in NKp30-positive andNKp46-positive NK cells.⑸After treatment, TRAIL and CD107a were markedly increased, suggested IFN-alphapromoted NK cell activation, caused to its cytotoxic function enhanced.⑹According to the therapeutic response, we further stratified the patients into the RVRand non-RVR groups, EVR and non-EVR, SVR and non-SVR. High frequency of NKG2A+NK cells is associated with the RVR and SVR of CHC patients. High frequency of NKG2A+and KIR2DL3+NK cells is associated with the EVR.⑺After standard IFN-alpha treatment, mainly by a rise in NKp30and a drop ofCD158b to promote NK cell activation; after Peg-interferon treatment, mainly by a rise ofNKp46and a drop of CD158a to promote NK cell activation.To sum up, NK cells play an important role in the pathogenesis and treatment of chronicHCV infection, IFN-α treatment promotes activation of the innate immune system, enhancesits ability to clear the virus.