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Two Methods of Heterokaryon Formation to Discover HCV Restriction Factors
Published on: July 16, 2012
Cellular immunity to hepatitis C virus core protein and the response to interferon in patients with chronic hepatitis
J J Lasarte1, M García-Granero, A López
1Department of Internal Medicine, Medical School and University Clinic, University of Navarra, Pamplona, Spain.
Insights
A robust T-helper cell response targeting hepatitis C virus (HCV) core antigens is crucial for viral clearance following interferon therapy. Higher precursor frequencies and broader epitope recognition correlate with sustained virological response.
Area of Science:
- Immunology
- Virology
- Hepatology
Background:
- Chronic hepatitis C virus (HCV) infection is a major global health concern.
- Interferon (IFN) therapy is a standard treatment, but predicting sustained response remains challenging.
- The role of T-cell immunity in achieving viral clearance after IFN therapy requires further elucidation.
Purpose of the Study:
- To investigate the association between T-cell responses against HCV core antigens and viral clearance after IFN therapy.
- To quantify the frequency of HCV core-specific T-helper (Th) cell precursors in patients undergoing IFN treatment.
- To analyze the recognition of specific HCV core epitopes by T-cells in relation to treatment outcomes.
Main Methods:
- Peripheral mononuclear cells from chronic hepatitis C patients were analyzed for interleukin-2 (IL-2) production in response to HCV core antigen.
- Limiting-dilution assays were used to determine the frequency of circulating core-specific Th cell precursors in a cohort of 43 patients.
- A second cohort of 60 patients had their response to 52 synthetic core peptides analyzed.
Main Results:
- Patients achieving sustained virological response (SR) exhibited significantly higher frequencies of core-specific Th cell precursors compared to untreated or non-responding patients.
- The number of recognized core peptides was substantially higher in SR patients (8.2) than in non-responders (2.0) or healthy controls (0.3).
- The intensity of T-cell proliferative response to core peptides was significantly higher in SR patients compared to non-responders and untreated patients.
Conclusions:
- Expansion of HCV-specific Th cell precursors is a critical factor for successful viral elimination post-IFN therapy.
- Effective clearance of HCV is associated with Th cell recognition of multiple HCV core epitopes.
- These findings highlight the importance of cellular immunity in achieving sustained virological response to IFN treatment for 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 core-specific T-helper (Th) cell precursors by the limiting-dilution 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 (IFN) therapy (median, 1/55,736) than in untreated patients (1/274,023) or that in patients who remained viremic after completion of the treatment-nonresponders (NR) plus transient responders (TR) (1/1,909,972). Patients who failed to respond to IFN (NR) and those who relapsed after IFN discontinuation (TR) had a similarly low number of precursors. The number of core peptides recognized by SR, TR, NR, UT, and healthy controls was 8.2 +/- 1.5, 6.5 +/- 1.2, 2.0 +/- 0.5, 2.7 +/- 0.9, and 0.3 +/- 0.2, respectively. In SR, the intensity of the proliferative response to core peptides as estimated by the summation of stimulation indexes (sigmaSI) was significantly higher than in NR and than in UT, but not different from that of TR. Our results indicate that both expansion of HCV-specific Th cell precursors and Th cell recognition of multiple core epitopes seem to be important in the elimination of HCV after IFN therapy.
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