Cellular immunity to hepatitis C virus core protein and the response to interferon in patients with chronic hepatitis C

Abstract

To investigate the involvement of T-cell response against hepatitis C virus (HCV) antigens in viral clearance after interferon therapy, we measured interleukin-2 (IL-2) production by peripheral mononuclear cells in response to HCV core in patients with chronic hepatitis C. In a cohort of 43 patients, we investigated the frequency of circulating corespecific T-helper (Th) cell precursors by the limitingdilution assay, and in a second cohort of 60 patients, we analyzed the response to specific core epitopes using 52 synthetic 15-mer overlapping peptides. We observed that the frequency of core-specific Th cell precursors was significantly higher in patients with sustained biochemical and virological response (SR) after interferon (

Specific and general HLA-DR binding motifs: comparison of algorithms

“…Thus, as described earlier, we deduced the algorithm DRGen shown in Table 5. This algorithm was then validated using several panels of peptides characterized by others [31,33,41], (Prof. Rammensee), as well as against 35 peptides from HCV core protein tested in the present study (Fig. 1).…”

“…Thirty-five 15-mer peptides from hepatitis C virus core protein genotype 1b [35] were synthesized manually by the solid phase method of Merrifield [36] using the Fmoc alternative [37] and a multiple solid phase peptide synthesizer [38]. Peptide HA(306 -320) (CPKYVKQNTL KLATG) from Influenza A/Texas/77 virus hemagglutinin was synthesized manually, and biotinylated (while still attached to the resin) with an excess of N-hydroxysuccinimide-conjugated biotin (NH-LC-biotin) (Pierce).…”

Enhancement of CD4 and CD8 immunity by anti-CD137 (4-1BB) monoclonal antibodies during hepatitis C vaccination with recombinant adenovirus

“…However, they are weak and inefficient [3][4][5][6][7][8][9][10]14,15,45]. In fact, the frequency of CTL precursors against HCV proteins found in patients with chronic hepatitis C is very low, in comparison to that found in HIV or CMV infections [46][47][48].…”

“…It is characterised by a high tendency to chronicity, which often progresses to cirrhosis and liver cancer [2]. Viral clearance after acute hepatitis or after IFN-␣ therapy is usually associated with strong CD4 and CD8 T cell responses [3][4][5][6][7][8][9][10][11][12]. In particular, cellular T helper immune response against nonstructural NS3 HCV protein has been associated with viral clearance after acute infection, whereas absence of this Tcell response leads to viral persistence and chronic hepatitis [9,13].…”

Antioxidant status and glutathione metabolism in peripheral blood mononuclear cells from patients with chronic hepatitis C

“…In previous work (16) we have found increased mRNA levels of manganese-dependent SOD (Mn-SOD) in peripheral blood mononuclear cells (PBMC) from patients with chronic HCV infection, suggesting that oxidative stress might be present in peripheral lymphocytes in this condition. Since the therapeutic response to IFN depends critically on the ability of this compound to stimulate an efficient antiviral immune response (17,18), and oxidative stress is known to impair the effector functions of lymphocytes (3), we decided to investigate further the presence of oxidative stress in PBMC from HCV-infected individuals. We therefore determined MDA, GSH and GSSG levels, GSH synthetic capability, mRNA expression for y-GCS, and the activities of SOD, catalase, GPX, GR and GST in peripheral blood mononuclear cells from patients with chronic hepatitis C and healthy controls.…”