Related Experiment Video
Updated: Aug 8, 2026
Immunofluorescence to Monitor the Cellular Uptake of Human Lactoferrin and its Associated Antiviral Activity Against the Hepatitis C Virus
Published on: October 1, 2015
Detection of functionally altered hepatitis C virus-specific CD4 T cells in acute and chronic hepatitis C
Axel Ulsenheimer1, J Tilman Gerlach, Norbert H Gruener
1Institute for Immunology, University of Munich, Germany.
Insights
In chronic hepatitis C, the immune system often fails to mount a robust CD4(+) T-cell response. This study reveals functional impairment and exhaustion of these critical T-cells, contributing to persistent hepatitis C virus (HCV) infection.
Area of Science:
- Immunology
- Virology
- Hepatology
Background:
- Chronic hepatitis C (HCV) infection is marked by a diminished HCV-specific CD4(+) T-cell response.
- Previous assessments relied on proliferation or cytokine secretion, potentially underestimating T-cell presence.
- Understanding the precise nature of T-cell dysfunction is crucial for explaining viral persistence.
Purpose of the Study:
- To determine if HCV-specific CD4(+) T cells are absent or functionally impaired in chronic hepatitis C.
- To characterize the activation status of CD4(+) T cells independent of cytokine production or proliferation.
- To compare T-cell responses in acute versus chronic hepatitis C.
Main Methods:
- Developed a novel assay measuring CD25 expression on activated CD4(+) T cells.
- Assessed antigen-specific T-cell proliferation, interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta) secretion.
- Analyzed T-cell responses in patients with acute and chronic hepatitis C.
Main Results:
- Activated HCV-specific CD4(+) T cells were detected in 10 of 20 chronic hepatitis C patients, but proliferation was rare (1/20).
- IFN-gamma secretion was absent in all tested chronic patients, while IL-10 and TGF-beta were secreted by some.
- Acute hepatitis C patients exhibited robust HCV-specific CD4(+) T-cell responses, which diminished over time in chronic cases, showing features of anergy or exhaustion.
Conclusions:
- Functional impairment and exhaustion of HCV-specific CD4(+) T cells contribute to viral persistence in chronic hepatitis C.
- The novel CD25-based assay effectively identifies antigen-specific activated T cells missed by traditional methods.
- Failure to establish a sustained T-helper response is a key factor in the chronicity of hepatitis C.
Abstract:
Chronic hepatitis C is characterized by a weak or absent hepatitis C virus (HCV)-specific CD4(+) T-cell response in terms of antigen-specific proliferation or interferon gamma (IFN-gamma) secretion. To clarify whether this is due to the absence or functional impairment of antigen-specific CD4(+) T cells we developed an assay that relies on the induced expression of the T-cell activation marker CD25 and is therefore independent from cytokine secretion or proliferation. In 10 of 20 patients with chronic hepatitis C, a significant number of antigen-specific activated CD4(+) T cells (mean 1.06%/patient; range, 0% to 5.2% of CD4(+) T cells) could be shown, whereas antigen-specific proliferation was present in only 1 of 20 patients. IFN-gamma secretion was absent in all 13 patients tested. However, significant antigen-specific interleukin 10 (IL-10) and transforming growth factor beta (TGF-beta) secretion was present in 6 of 10 and 3 of 10 patients, respectively. In 8 patients with acute hepatitis C, irrespective of disease outcome, HCV-specific CD4(+) T cells were detected in all patients and at a significantly higher frequency (mean 3.7%/patient; range, 1.16% to 7.17%) in the first weeks of disease. A chronic course of disease was associated either with a loss of both IFN-gamma secretion and proliferation, resembling an anergic state, or a loss of T-cell proliferation followed by a rapid decline in IFN-gamma-producing cells, corresponding to exhaustion of the specific immune response. In conclusion, functional changes of HCV-specific CD4(+) T cells or failure to develop a long-lasting T-helper response may contribute to chronic hepatitis C viral persistence.
