Decrease in CD3-negative-CD8dim + and Vδ2/Vγ9 TcR+ peripheral blood lymphocyte counts, low perforin expression and the impairment of natural killer cell activity is associated with chronic hepatitis C virus infection

Abstract

Background/Aims: As chronic hepatitis C virus (HCV) infection is associated with impaired natural killer (NK) cell cytotoxicity, we examined the phenotypes and perforin expression of peripheral blood lymphocytes, as well as the effect of interferon-α2b (IFN-α2b) therapy. Methods: Thirty-three patients had chronic hepatitis C, and of them 12 had been on IFN-α2b treatment. Eleven individuals had been treated earlier with IFN-α2b and completely cured, and eight were HCV carriers with persistently normal serum alanine aminotransferase. Three-colour flow cytometry was used to measure the percentage of CD3 +/−CD8+, CD3+CD4+, γδTcR+, Vδ2 TcR+, Vγ9 TcR+, Vδ1 TcR+, CD3−CD16+, CD3−CD56+, CD19+ and perforin-positive cells. NK cell activity was assessed by single cell cytotoxic and flow cytometric assay. Results: Patients with chronic hepatitis C showed an impaired NK cytotoxicity, decreased percentage of CD3-negative-CD8dim-positive (NK subtype) and Vγ9/Vδ2 TcR+ as well as perforin-positive T lymphocytes, compared to controls and to those who were cured from HCV infection. IFN-α2b increased NK cell cytotoxicity and the percentage of perforin-positive lymphocytes. Conclusions: Our findings suggest that in chronic HCV infection a decreased percentage of CD3 −CD8+, Vγ9/Vδ2 TcR+ and perforin-positive T cells and simultaneous decreased peripheral NK activity may contribute to the impaired cellular immune response and the chronicity of the disease.