CHARACTERIZATION OF HBV-SPECIFIC T CELL DYSFUNCTION IN CHRONIC HBV INFECTION.
J Virol. 2007 Feb 7
Boni C, Fisicaro P, Valdatta C, Amadei B, Di Vincenzo P, Giuberti T, Laccabue D, Zerbini A, Cavalli A, Missale G, Bertoletti A, Ferrari C.
Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Italy; Centre of Molecular Medicine, Agency for Science, Technology and Research, Singapore.
Dysfunctional CD8+ T cells present in chronic virus infections can express PD-1 molecules and the inhibition of PD-1 engagement with its ligand (PD-L1) has been reported to enhance their anti-viral function. We took advantage of the wide fluctuations of viremia which are typical of chronic HBV infection to comprehensively analyze the impact of prolonged exposure to different virus quantities on virus-specific T cell dysfunction and on its reversibility through blockade of the PD-1/PD-L1 pathway. We confirm that chronic HBV infection has a profound effect on the HBV-specific T cell repertoire. Despite the use of a comprehensive panel of peptides covering all HBV proteins, HBV-specific T cells were rarely observed directly ex vivo in chronic patients, in contrast to patients with acute HBV infection. In chronic HBV infection virus-specific T cells were mainly detected in patients with lower viremia. These HBV-specific CD8+ T cells expressed PD-1, and their function was improved by blocking PD-1/PD-L1 engagement. Thus, a broad spectrum of anti-HBV immunity is expressed by patients with chronic HBV infection, which is proportional to HBV replication levels and can be improved by blocking the PD-1/PD-L1 pathway. This information may be useful for the design of immunotherapeutic strategies to complement and optimize available anti-viral therapies. |
