In a setting of HCMV reactivation following solid organ transplantation, Lopez-Verges et al. recently described that NK cells change their phenotype and undergo differentiation during expansion as illustrated by the expression of CD57 23. Hence, although NKG2C and KIRs are likely expressed from the start it cannot be excluded

that cells are further shaped during the immune response. The comparison of NK-cell expansion with the clonal expansion of T cells is interesting and was recently reviewed 45. Although we have borrowed the term ‘clonal expansion’ from the expansion of T cells following antigen Rapamycin stimulation in the lymph node, there are several major differences between the two processes

and we do not infer similar mechanisms. In fact, we cannot formally prove that cells have expanded clonally. It is possible that distinct NK cells, expressing the same advantageous KIR, expand in parallel. However, we favor the interpretation that there is a clonal expansion of NK cells having a particular setup of KIRs. NKG2C expression in healthy donors has been detected only in relation to HCMV, but not EBV or HSV seropositivity 16, 46. Similarly, during both acute hantavirus and HIV-1 infection, NKG2C increases only in patients that are seropositive for HCMV 18, 19. Previous studies, reporting on the increase of NKG2C+ NK cells in chronic HBV or HCV infections, have not taken HCMV serostatus into account XAV-939 manufacturer 20, 21. Here, we show that high NKG2C expression was associated with HCMV seropositivity also in these two chronic liver infections. Because of the unusually high frequency of HCMV positive in the studied cohorts, the role of HCV and HBV infection alone on NKG2C expression was somewhat difficult to evaluate. Nevertheless, none of the HCMV-negative

hepatitis virus-infected patients (n=6) displayed significant levels of NKG2C+ NK cells suggesting that the expansion of this subset is dependent on HCMV. Our data prompt Ixazomib nmr for further studies to delineate the role of chronic HCV/HBV infection per se, on the expansion of NKG2C+ NK cells. It has been observed, both in vitro and in vivo, that hepatocytes are permissive for HCMV infection 47. Other studies suggest that chronic HBV and HCV infections might be associated with frequent HCMV reactivation in the liver 24, and that liver cirrhosis induced by HCV infection is associated with HCMV reactivation in peripheral blood 25. In the present study, quantitative PCR did not show HCMV reactivation in either peripheral blood or in the liver of HBV- or HCV-infected patients. Moreover, the frequencies of NKG2C+ NK cells in our cohorts does not seem to differ significantly from those of previous investigations in healthy controls 16, 18, 22.