Differential T cell subset activation in patients with different outcomes of hepatitis C

Abstract

Backoround: A differential activation of T ceil subsets and cytokine induction may be responsible for different outcomes in hepatitis C. Method: We analyzed the hepatitis C (HCV) specific immune response to the recombinant HCV proteins core, NS3, NS4, NS5a and NS5b in peripheral blood lymphocytes (PBL) of 29 patients with chronic hepatitis C (group 1) and 8 patients with Self-limited HCV infection (group2). T-cell subset expansion of the common T-cell receptors VI32, VI33, VI35, VI36.1, VI38, VI313.1, V[313.6, VI314, VI317, VI321.3 as well as intracytoplasmic expression of IL-2, IFN-y, TNF-ct, IL-4 and IL-10 were determined in CD45RO ÷ T cells at the single cell level by fluorescence activated cell sorting. Data are given as mean stimulation index with standard error of the mean (SI-+ SEM) and statistical analysis was done by Mann-Whitney U test. Results: In patients with chronic hepatitis C the TCR V~8 + subset expanded significantly after stimulation with all HCV proteins (p<0.05, groupl vs. group2, SI -+ SEM: Core: 3.1 -+ 1.1 vs. 0.7 -+ 0.1, NS3 4.7 2.2 vs. 0.8 -+ 0.2, NS4 3.8 -+ 1.5 vs. 1.1 +0.7, NS5a 5.9 -+ 1.9 vs. 0.8 -+ 0.1, NS5b 8.6 -+ 3.1 vs. 1.0 -+ 0.2). By contrast, after stimulation with NS3 VI32 + and VI36.1 ÷ T cells expanded significantly in patients of group 2 (p<0.05, groupl vs. group2: V132 0.9 + 0,1 vs. 1.5 -+ 0.4, VI36.1 0.8 +-. 0,1 vs. 2.9 -+ 0.7). In this group TCR V132 +, V1314 + and V1321.3 ÷ T cells were also induced significantly after stimulation with NS5b (p<0.05, groupl vs. group2:VI32 1.0-+0.1 vs. 1.7-+0.3, VI314 0.9-+0.1 vs. 3.6-+1.5, V1321.3 1.1-+0.1 vs. 2.0+0.4). All other tested T cell subsets did not expand significantly after stimulation with hepatitis C proteins in both patient groups. In group 2 the simultaneous analysis of cytokines revealed a stronger IL-2 response (p<0.05) after stimulation with all HCV proteins, a stronger IFN-7 (p<0.05) and TNF-ct (p<0.05) response to core and NS3 protein. However, a preferential cytokine production could not be allocated to expansion of a particular T cell subset. Conclusion: Our data indicate differential HCV-specific expansion of T cell subsets, which may be related to the different outcome of HCV infection in our two groups. However, these differences in the activation of T cell subsets do not explain the preferential type 1 cytokine pattern in patients with selflimited disease.