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Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice
Published on: September 25, 2019
CD4+/CD25+ T cells suppress autologous CD4+/CD25- lymphocytes and secrete granzyme B during acute and chronic
Alessandro Perrella1, Anna D'Antonio, Costanza Sbreglia
1VII Department of Infectious Disease and Immunology, Hospital D. Cotugno, Naples, Italy.
Insights
Patients with acute and chronic hepatitis C exhibit increased regulatory T (Treg) cells that secrete Granzyme B (GZB), potentially inducing apoptosis. This contrasts with healthy individuals and those who resolve hepatitis C virus infection.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- Hepatitis C virus (HCV) infection is a major global health concern.
- The role of regulatory T (Treg) cells in HCV pathogenesis remains incompletely understood.
- CD4(+)CD25(+) Treg cells are crucial for immune homeostasis and can suppress immune responses.
Purpose of the Study:
- To investigate the frequency and function of CD4(+)CD25(+) Treg cells in patients with acute and chronic hepatitis C (CHC).
- To determine if these Treg cells secrete Granzyme B (GZB) during HCV infection.
- To assess the correlation between Treg cell activity, GZB production, and apoptosis markers.
Main Methods:
- Analysis of peripheral blood from 50 subjects: 20 CHC patients, 15 healthy controls, 10 acute hepatitis C patients, and 5 resolved HCV cases.
- Quantification of CD4(+)CD25(+) Treg cell frequency and function.
- Measurement of Granzyme B (GZB) spot-forming colonies (SFCs).
- Assessment of Annexin V activity as an apoptosis marker.
Main Results:
- Patients with acute and chronic hepatitis C showed significantly higher frequencies and functions of peripheral Treg cells compared to healthy controls.
- Increased GZB secretion (SFCs) was observed in Treg cells from acute and chronic hepatitis C patients versus healthy individuals.
- Treg cells from patients who resolved HCV infection had lower GZB SFCs than those with persistent infection but higher than healthy controls.
- Higher Annexin V production, indicating apoptosis, was noted in patients with acute and chronic hepatitis C.
Conclusions:
- Elevated Treg cell frequency and function, along with increased GZB secretion, are characteristic of acute and chronic hepatitis C.
- These findings suggest that Treg cells may contribute to viral persistence and immune evasion in HCV infection by inducing apoptosis.
- Understanding Treg cell dynamics in HCV is crucial for developing targeted immunotherapies.
Abstract:
We aimed to verify whether CD4(+)/CD25(+) T cells suppress CD4(+) T cells and secrete Granzyme B (GZB) during acute and chronic hepatitis C (CHC) infection. We enrolled 50 subjects: 20 patients with CHC (Group A), 15 healthy individuals (Group B), 10 patients with acute hepatitis C later evolved to persistent infection (Group C) and five patients who resolved hepatitis C virus infection during acute phase (Group D). We analysed, on enrolled subjects CD4(+)/CD25(+) T cells and related GZB production as well as Annexin V activity. Patients from Groups A and C had higher frequency and function of peripheral Treg cells than healthy individuals. Groups A and C showed an increase in spot-forming colonies (SFCs) of GZB compared with Group B (P < 0.01, Mann-Whitney U-test). CD4(+)/CD25(+) T cells in Group D had a lower number of GZB SFCs compared with Groups A and C but higher number than Group B (P < 0.01 Mann-Whitney U-test). Annexin V production was higher in Groups A and C than B or D. Patients having acute and chronic hepatitis C have a higher Treg frequency and function in peripheral blood than healthy controls or those resolving the infection in acute phase secreting GZB, probably inducing apoptosis.
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