However, the differences of immunological derangements underlying this phenomenon aroused by different
HCV serotypes are not yet elucidated. Here we focused on natural killer group 2, member D (NKG2D), an activating receptor exerting cytotoxicity or IFN-γ secretion to virus-infected cells, and analyzed NKG2D expression on natural killer (NK) cells, NKT cells and CD8 T lymphocytes Selleck BYL719 in serotype 1 and 2 HCV infections, to examine how differential NKG2D expression on NKT cells predicts response to IFN-based therapy. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from patients of chronic persistent hepatitis C, fifty-three with serotype 1, and thirteen with serotype 2 infection, with informed consent, and were analyzed for pre-treatment 5-Fluoracil datasheet NKG2D expression by flow cytometry. IFN-γ secretion ability was analyzed ex vivo after PMA/Ino-mycin stimulation. Finally, Two strains of HCV, JFH1 (genotype 2a) and TNS2J1 (1b in structural region and 2a in non-structural region, J Virol 2009. 83, p6922–6928) were co-cultured them with PBMCs to prove the phenomenon we observed. Results: NKG2D expression levels on NKT cells, but not on NK cells, were significantly decreased
in HCV serotype 1 infection (71.4± 1.6%) compared to serotype 2 infection (87.8± 3.2%, p< 0.0001). Regardless of serotype differences, the level of NKG2D expression on NKT cells Chorioepithelioma showed high and significant positive correlation to the level of HCV-RNA drop from week 0 to week 4 (correlation coefficient, 0.81; P< 0.0001). Significant differences of the level of NKG2D expression on NKT cells between SVR and otherwise
cases were also noticed. NKG2D expression on NKT cells showed no difference when stratified neither with IL28B SNPs nor with ISDR mutation numbers, however, showed significant difference when stratified with core protein determination at aa70 and aa91. In ex vivo stimulation study, decreased NKG2D expression on NKT cells highly and significantly correlated to its impaired IFN-γ production (correlation coefficient, 0.89; p < 0.0001). In co-culture study, NKG2D expression levels on NKT cells significant decreased in TNS2J1 (1b/2a) group, but not in JFH1 (2a) group. This phenomenon was not noticed in NK cells. Conclusion: HCV serotype 1 viral infection causes impaired NKG2D expression on NKT cells, but not NK cells, compared to serotype 2. This differential levels of NKG2D expression on NKT cells predict diminished on-treatment peripheral HCV RNA decrease, and therefore, inferior response to IFN-based therapy.