Alterations Of NK Cell Frequency And Function In HIV/HCV Co-infected Patients

Objective:To evaluate the frequency, CD107a/IFN-y secreting ability and killing function of NK cells in HIV/HCV co-infected patients,explore the influence of NK cell on HIV/HCV co-infection,discuss the role of NK cells in the immune response of co-infection and its impact on the development of liver disease.Methods:18 case of HIV/HCV co-infeced patients,30 case of HIV single infected patients,20 case of HCV single infected patients,and 18 case of healthy donors were included. Analyses were performed to clear the difference of the demographic data,time for infection,level of ALT/AST,viral load of HIV or HCV,and count of CD4+T cells among each group.Peripheral blood mononuclear cells(PBMCs) were isolated,NK cells were counted by using flow cytometry (FCM).Stimulated with IL-12/15,PMA and K562 cells, PBMCs were dectected to investigate the proportion of CD107a+NK cells and IFN-y+NK cells.Under different E/T ratios, cytolytic activity of NK cells was tested by killing K562 cells. Statistical analyses were performed with the CHISS 2004 statistical software. Results were considered significant at the two sided p level of 0.05.Results:In HIV/HCV co-infection group and single HIV or HCV infection group, percentage and absolute count of NK cells were significantly lower than that in the health control group; there was no significant differences in the proportion of NK cells among single HIV infection group, single HCV infection group and HIV/HCV co-infection group,but the absolute count of NK cells in co-infection was lower than that in single infection with HIV or HCV[(142±69)/ul vs (199±56)/ul vs (207±68)/ul, p<0.05].Stimulated with IL-12/15, the proportion of CD107a+NK cells in co-infection group was lower than that in single HCV infection group, the proportion of IFN-y+NK cells in this group was higher than that in single HIV infection group. Stimulated with PMA,the proportion of IFN-y+NK cells in co-infection group and single HIV or HCV infection group were lower than that in health control group,but there was no significant differences in this index among the three viral infeciton group.The proportion of. CD107a+NK cells and IFN-y+NK cells in lymphocyte has the same law to the frequency of NK cells,is that the three viral infection group had lower proportion than health control group,and co-infection group has lower propotion than single HIV or HCV infection group.In the experiment of NK cells killing function, we found that along with the increase of E/T ratios,the proportion of killed K562 cells were gradually increased.When the E/T ratio was 10:1, there was no significant differences in proportion of killed K562 cells among co-infection and single HIV or HCV infection,but when the E/T ratio was 30:1,this index in co-infection[(7.229±2.545)%] were significantly lower than that in single HIV infection[(13.451±8.802)%,p<0.05] and single HCV infection[(12.989±9.563) %, p>0.05].Conclusion:This study shows that the frequency and function of NK cells in HIV HCV co-infected patients were significantly lower than those in HIV or HCV single infected patients. The reason of this diversity and the mechanism of interaction between HIV and HCV need further study.Result of our study indicates that the decreased frequency and impaired function maybe induce the aggravated liver injury in co-infected patients, and provide evidence for the further probalble NK cell immunotherapy for co-infected patients.