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Analysis of HBV-Specific CD4 T-cell Responses and Identification of HLA-DR-Restricted CD4 T-Cell Epitopes Based on a Peptide Matrix
Published on: October 20, 2021
Decrease and dysfunction of dendritic cells correlate with impaired hepatitis C virus-specific CD4+ T-cell
Silvia Della Bella1, Andrea Crosignani, Antonio Riva
1Dipartimento di Scienze e Tecnologie Biomediche, Cattedra di Immunologia, Università degli Studi di Milano, Milan, Italy. silvia.dellabella@unimi.it
Dendritic cells (DCs) play a key role in regulating immune responses to hepatitis C virus (HCV). In chronic HCV infection, peripheral blood DCs (PBDCs) are reduced and show altered cytokine profiles, impacting T-cell responses.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Dendritic cells (DCs) are crucial for initiating and regulating virus-specific immune responses.
- Hepatitis C virus (HCV) infection can lead to chronic disease, characterized by impaired immune control.
- The role of peripheral blood dendritic cells (PBDCs) in the persistence of HCV infection requires further investigation.
Purpose of the Study:
- To investigate the characteristics of PBDCs in patients with chronic hepatitis C (CHC).
- To compare PBDCs in CHC patients with those in healthy seronegative (HSN) individuals and those who spontaneously resolved HCV infection (HSP).
- To evaluate the relationship between PBDC function and HCV-specific CD4(+) T-cell reactivity.
Main Methods:
- Flow cytometry was used to analyze the number, immunophenotype, and cytokine expression (IL-12, IL-10) of PBDCs in whole-blood samples.
- Peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with HCV peptides to assess HCV-specific CD4(+) T-cell activation, proliferation, and cytokine production.
Main Results:
- PBDCs were numerically reduced in CHC patients compared to HSN controls.
- PBDCs from CHC patients exhibited lower interleukin-12 (IL-12) and higher interleukin-10 (IL-10) expression than those from HSN controls.
- HSP subjects had PBDC profiles similar to HSN controls, and HCV-specific CD4(+) T-cell proliferation was impaired in CHC patients, correlating inversely with IL-10 and directly with PBDC number and IL-12 production.
Conclusions:
- Altered PBDC numbers and cytokine profiles (reduced IL-12, increased IL-10) in CHC patients contribute to the dysregulation of HCV-specific immunity.
- PBDCs may serve as a potential non-invasive biomarker for immune monitoring in patients with chronic hepatitis C.
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