Detection of type 2‐like T‐helper cells in hepatitis C virus infection: Implications for hepatitis C virus chronicity

• Published in: Hepatology (Baltimore, Md.) Vol. 25; no. 2; pp. 449 - 458
• Main Authors: Tsai, S, Liaw, Y, Chen, M, Huang, C, Kuo, G C
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.02.1997; Wiley
• Subjects: Adult; Aged; AIDS/HIV; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Female; Hepatitis C - immunology; Hepatitis, Chronic - immunology; Human viral diseases; Humans; Infectious diseases; Interferon-gamma - pharmacology; Interleukin-10 - pharmacology; Interleukin-2 - pharmacology; Interleukin-4 - pharmacology; Lymphocyte Activation - drug effects; Male; Medical sciences; Middle Aged; Th2 Cells - drug effects; Th2 Cells - immunology; Th2 Cells - physiology; Viral diseases; Viral hepatitis; Infection; Human; Chronicity; Viral disease; T-Lymphocyte; Digestive diseases; Hepatic disease; Helper cell; Evolution; Viral hepatitis C
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.510250233

One striking clinical feature of hepatitis C virus (HCV) infection is that more than 50% of patients with acute hepatitis C will develop chronic infection. To investigate its possible mechanisms, we examined the activation of type 2‐like T‐helper (Th2‐like) cells relating to the development of chronicity. Peripheral blood CD4+ T‐cell proliferation and cytokine secretion in response to a panel of recombinant HCV antigens including core (C22), envelope 1 (E1), E2, nonstructural (NS) protein 4 (C100), fusion protein of NS3 and NS4 (C200), and NS5 were assayed in 17 patients with acute hepatitis C. All six patients with self‐limited disease had a significant CD4+ T‐cell proliferation to C22, E1, C100, C200, and NS5, running parallel with the antigen‐stimulated secretion of interleukin (IL)‐2 and interferon γ (IFN‐γ), but not with interleukin (IL)‐4 and IL‐10, indicating predominant Th1 responses. Among the remaining 11 patients who developed chronicity, 6, 2, and 9 cases showed a specific CD4+ T‐cell response to C22, C100, and C200, respectively, and the responses were significantly lower than those of cases with recovery in terms of stimulation index (SI) (P < .05) and of antigen‐stimulated IL‐2 and IFN‐γ production. Importantly, IL‐4 and IL‐10 (Th2 responses) were detectable, and C22‐specific Th2‐like T‐cell clones could be generated from patients with chronicity. The data suggested that activation of Th2 responses in acute hepatitis C patients may play a role in the development of chronicity.