The Impact Of The Tim-3、PD-1and CD28Expressions On The Hepatic Inkt Cell Functions In Chronic Hepatitis B Patients

In this study we tried to explore the impact of the Tim3、PD1andCD28expressions on the hepatic iNKT cell functions in Chronic hepatitisB patients. Healthy donors and chronic hepatitis B patients were compared.First we constructed a method for expanding iNKT cells on chronic HBVinfection with α-galactosylceramide(α-GalCer) ex vivo. Flow cytometrywas then used to detect the hepatic iNKT frequencies and the Tim-3, PD-1,CD28, IL-4and IFN-γ levels secreted by the hepatic iNKTs, and ELISAwas used to identify the IL-4and IFN-γ secretions on α-GalCer activationex vivo. As a result, the frequency of the iNKT cells in chronic hepatitis Bpatients’ livers was significantly decreased as compared with that in healthydonors（P＜0.05）. Moreover, the expressions of the inhibitory Tim-3andPD-1on hepatic iNKT cells were much higher but the expression of thecostimulant CD28was much lower as compared with the healthy donors（P＜0.05）, The IL-4and IFN-γ productions by hepatic iNKT cells fromchronic hepatitis B patients were also much lower than that from healthydonors （P＜0.05）. When the iNKT cells were co-activated withα-GalCer/anti-Tim-3/anti-PDL1/anti-CD28/CD80for72hours, the IFN-γ and IL-4productions were dramatically increased as compared to that ofbefore activation（P＜0.05）. This study suggested that iNKT cells playedan important role in the chronic HBV infection and the iNKT functionalimpairment could closely related with the decrease of costimulant CD28expression and the increase of the inhibitory Tim-3and PD-1expressions.