1. Memory T Cell Proliferation before Hepatitis C Virus Therapy Predicts Antiviral Immune Responses and Treatment Success
- Author
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Méndez-Lagares, Gema, Lu, Ding, Chen, Connie, Terrault, Norah, Segal, Mark R, Khalili, Mandana, Monto, Alexander, Shen, Hui, Manos, M Michele, Lanier, Lewis L, Ryan, James C, McCune, Joseph M, and Hartigan-O'Connor, Dennis J
- Subjects
Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Prevention ,Infectious Diseases ,Immunization ,Hepatitis - C ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Emerging Infectious Diseases ,Digestive Diseases ,Vaccine Related ,Clinical Research ,Hepatitis ,Inflammatory and immune system ,Infection ,Good Health and Well Being ,Adaptive Immunity ,Antibodies ,Viral ,Antiviral Agents ,CD4-Positive T-Lymphocytes ,Cell Proliferation ,Drug Therapy ,Combination ,Female ,Hepacivirus ,Hepatitis C ,Chronic ,Humans ,Immunity ,Innate ,Immunologic Memory ,Interferon-alpha ,Longitudinal Studies ,Lymphocyte Activation ,Male ,Middle Aged ,Oligopeptides ,Polyethylene Glycols ,Proline ,Prospective Studies ,Recombinant Proteins ,Ribavirin ,T-Box Domain Proteins ,Treatment Outcome ,Biochemistry and cell biology - Abstract
The contribution of the host immune system to the efficacy of new anti-hepatitis C virus (HCV) drugs is unclear. We undertook a longitudinal prospective study of 33 individuals with chronic HCV treated with combination pegylated IFN-α, ribavirin, and telaprevir/boceprevir. We characterized innate and adaptive immune cells to determine whether kinetics of the host response could predict sustained virologic response (SVR). We show that characteristics of the host immune system present before treatment were correlated with successful therapy. Augmentation of adaptive immune responses during therapy was more impressive among those achieving SVR. Most importantly, active memory T cell proliferation before therapy predicted SVR and was associated with the magnitude of the HCV-specific responses at week 12 after treatment start. After therapy initiation, the most important correlate of success was minimal monocyte activation, as predicted by previous in vitro work. In addition, subjects achieving SVR had increasing expression of the transcription factor T-bet, a driver of Th1 differentiation and cytotoxic effector cell maturation. These results show that host immune features present before treatment initiation predict SVR and eventual development of a higher frequency of functional virus-specific cells in blood. Such host characteristics may also be required for successful vaccine-mediated protection.
- Published
- 2018