Bedeutung von natürlichen Killer T-Zellen in der chronischen Hepatitis C Infektion
Final Report Abstract
During my postdoctoral fellowship at the National Institutes of Health I demonstrated that low-dose exposure to Hepatitis C virus (HCV) activates innate and adaptive cellular immune responses, which may contribute to the prevention of high-level systemic viremia and acute liver disease. The multifunctional NK cell response (cytotoxicity and IFN-γ production) in these HCV-exposed healthcare workers differed from the impaired NK cell response (increase in cytotoxicity and decrease in IFN-γ production) in chronic HCV infection. In a follow up study we were able to identify monocyte derived IL-18 as a link between monocyte activation and IFNγ production from NK cells. This finding suggests that the impaired NK cell function in chronic HCV may rather due to decreased IL-18 production from monocytes than a NK cell defect itself. In a second research project, I studied the longevity of immune protection in health care workers who have been vaccinated against HBV as adults. 10-28 years after vaccination sixty-five percent displayed anti-HBs levels above the cut-off of >12 mIU/ml, which is a similar frequency compared to studies following vaccinated infants. Interestingly, occupational HBV exposure after vaccination did not induce anti-HBc, the standard biomarker for HBV infection, but HBcore and HBVpolymerase-specific CD4 and CD8 T cells. Vaccinees with anti-HBs titers below 12 mIU/ml were offered a booster vaccination, and their baseline frequency of IFN-γpositive HBs-specific T cells correlated to the booster-induced antibody response. In conclusion, HBsAg vaccination does not induce sterilizing immunity as evidenced by HBcore- and HBVpolymerase-specific T cells after occupational exposure. However, the absence of chronic infection in all vaccinated health care workers and the rapidity of the booster response in those that had lost anti-HBs are both strong indicators of protective immunity.
