Centre for Biomedical Research, Burnet Institute, Melbourne, Australia; Department of Immunology, Monash University, Melbourne, Australia. firstname.lastname@example.org.
BACKGROUND AND AIM:
T cell responses against hepatitis C are believed to be critical in achieving both natural and treatment induced clearance. However, rapid clearance of antigen with early treatment of primary infection may result in reduced or poorly sustained cellular immunity. This study longitudinally examined Th1 and Th2 HCV-specific cytokine production and T cell effector function from subjects enrolled in the Australian Trial in Acute Hepatitis C (ATAHC) comparing three groups: treatment-induced clearance (sustained virological response [SVR]), treatment non-response, and untreated spontaneous clearance.
HCV-specific T cell responses were characterised by HCV peptide ELISpot, in-vitro cytokine production and T cell flow cytometry assays.
Treated subjects with a SVR displayed a better maintenance of HCV-specific Th1 responses compared to treatment non-responders (higher interferon (IFN)-γ and interleukin (IL)-2 magnitude week 24, broader IFN-γ responses week 24 and 48, p<0.05), and significantly increased IFN-γ responses between screening and week 48 (magnitude p=0.026, breadth p=0.009). Treatment-induced viral clearance was also associated with a trend towards decreased IL-10 responses (screening to week 48 p=0.070), higher expression of CD45RO (p=0.042) and CD38 (p=0.088) on CD4+ T cells and higher IFN-γR expression (CD56+ IFN-γR+ p=0.033) compared to treatment non-responders. Untreated subjects with viral clearance also displayed high magnitude and broad HCV-specific IFN-γ and IL-2 responses early in infection, however IFN-γ responses were not as well maintained compared to treated subjects with a SVR (week 48 magnitude, breadth p=0.064).
Treatment-induced viral clearance of recent HCV infection is associated with maintenance of HCV-specific Th1 responses.