Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source...

Area of Science:

• Immunology
• Virology
• Hepatology

Background:

• Acute hepatitis C virus (HCV) infection is often asymptomatic, making immune correlates of recovery poorly understood.
• Current diagnosis of resolved HCV relies on antibody detection and absence of viral RNA, limiting detailed immune response comparisons.
• Previous studies faced challenges due to heterogeneous patient cohorts, HCV strains, and lack of long-term follow-up data.

Purpose of the Study:

• To investigate the long-term persistence of humoral and cellular immune responses following recovery from acute hepatitis C.
• To identify reliable biomarkers for past HCV exposure and self-limited infection.

Main Methods:

• Studied a cohort of women with accidental exposure to a single, known HCV strain.
• Assessed HCV-specific antibodies and T-cell responses (helper and cytotoxic) with interferon-gamma (IFN-γ) production (Tc1 phenotype) 18-20 years post-recovery.
• Compared antibody levels with cellular immune responses in recovered individuals.

Main Results:

• HCV-specific antibodies were undetectable in many patients 18-20 years after recovery.
• HCV-specific CD4+ helper and CD8+ cytotoxic T-cell responses (Tc1 phenotype) persisted long-term.
• Persistent T-cell responses were observed even when antibodies were absent.

Conclusions:

• HCV-specific CD4+ and CD8+ T cells are robust biomarkers of prior HCV exposure and recovery.
• The persistence of cellular immunity suggests a more comprehensive understanding of self-limited HCV infections is needed.
• The incidence of resolved HCV infections may be underestimated due to reliance on antibody detection.