T helper, cytotoxic T lymphocyte, NK cell and NK-T cell subpopulations in patients with chronic hepatitis C.

Abstract

The phenotype of intrahepatic (IHL) and peripheral blood lymphocytes (PBL) was determined, and the production of cytokines by T lymphocytes analyzed in patients with chronic hepatitis C (CHC). Three-color fluorescence-activated cytometric analysis was done for 36 patients with untreated CHC. The percentage of peripheral blood memory T cells was higher in patients with CHC than in healthy controls (all data in %, significant at p < 0.001; 74.6 +/- 2.7 vs. 58.3 +/- 4.5), and a greater proportion of them were observed in the intrahepatic compartment (IHL-94.2 +/- 2.8 vs. PBL-74.6 +/- 2.7). There was a higher percentage of peripheral blood T helper 1 lymphocytes expressing IFN-gamma (IFN-gamma/IL-4) in these patients (4.6 +/- 0.7 vs. control-2.2 +/- 0.5). The expression of CXCR3 chemokine receptors on peripheral blood T helper cells was also high compared with the control (39.8 +/- 4.8 vs. 26.8 +/- 2.5) and a large percentage of T cells expressing CXCR3 or CCR5 chemokine receptors was observed in hepatitis C virus (HCV)-infected liver (CXCR3: IHL vs. PBL-74.9 +/- 5.7 vs. 39.8 +/- 4.8; CCR5: IHL vs. PBL-65.9 +/- 5.9 vs. 19.1 +/- 2.1). The intrahepatic compartment contains a greater proportion of activated cytotoxic T lymphocytes (CTL) and natural killer-T (NK-T) cells than peripheral blood (CTL: IHL vs. PBL-69.5 +/- 3.2 vs. 59.9 +/- 3.1; NK-T: IHL vs. PBL-10.6 +/- 2.5 vs. PBL: 3.99 +/- 0.5). The data suggest that in HCV-infected subjects, memory TH1 lymphocytes, activated CTL and NK-T cells compartmentalize in liver tissue and could play an important role in pathogenesis of chronic hepatitis.