Quantitative and functional analysis of core-specific T-helper cell and CTL activities in acute and chronic hepatitis B

Aims/Background: CD4(+) T-helper cell (Th) responses to hepatitis B virus ( HBV) core antigen (HBc) are increased during exacerbations in acute and chr onic hepatitis B (AHB, CHB) and might influence the induction of CD8(+) cyt otoxic T lymphocytes (CTL) that are important for viral clearance. Methods. HBc-specific proliferative responses and cytokine release of blood mononuc lear cells (PBMC) were studied in patients with AHB or CHB, as well as resp onders and non-responders to interferon-cc treatment (IFN-R, IFN-NR), by [H -3]-thymidine-uptake, enzyme-linked immunosorbent assay (ELISA) and Elispot assay and were compared to peptide HBc18-27-specific CTL precursor frequen cies among CD8(+) T cells derived from HLA-A2(+) patients. Results. HBc-spe cific proliferative PBMC responses and Th frequencies were significantly in creased in AHB patients compared with untreated CHB patients. PBMC derived from IFN-R showed stronger cellular responses than IFN-NR. Stimulated PBMC from all patient groups secreted significantly more IFN-gamma than IL-4 ind icating Th1/Th0 cell responses. Furthermore, in AHB and IFN-R patients, hig h peptide HBc18-27-specific CTL precursor frequencies closely correlated wi th strong HBc-specific Th responses, whereas in untreated CHB and IFN-NR pa tients lower CTL frequencies were observed without correlation to Th activi ties. Conclusions. HBV core-specific Th-cell responses appeared to support efficient CTL induction in patients with viral clearance, whereas in chroni c HBV carriers quantitatively insufficient Th and CTL responses were observ ed. This observation could be important for future therapeutic strategies.