Memory t cell proliferation before hepatitis c virus therapy predicts antiviral immune responses and treatment success

Gema Méndez-Lagares, Ding Lu, Connie Chen, Norah Terrault, Mark R. Segal, Mandana Khalili, Alexander Monto, Hui Shen, M. Michele Manos, Lewis L. Lanier, James C. Ryan, Joseph M. McCune, Dennis Hartigan-O'Connor

Research output: Contribution to journalArticle

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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-a, 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.

Original languageEnglish (US)
Pages (from-to)1124-1132
Number of pages9
JournalJournal of Immunology
Volume200
Issue number3
DOIs
StatePublished - Feb 1 2018

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Hepatitis Viruses
Antiviral Agents
Cell Proliferation
Hepacivirus
Immune System
Therapeutics
Ribavirin
Adaptive Immunity
Chronic Hepatitis C
Longitudinal Studies
Monocytes
Blood Cells
Vaccines
Sustained Virologic Response
Prospective Studies
Viruses
T-Lymphocytes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology

Cite this

Memory t cell proliferation before hepatitis c virus therapy predicts antiviral immune responses and treatment success. / Méndez-Lagares, Gema; Lu, Ding; Chen, Connie; Terrault, Norah; Segal, Mark R.; Khalili, Mandana; Monto, Alexander; Shen, Hui; Michele Manos, M.; Lanier, Lewis L.; Ryan, James C.; McCune, Joseph M.; Hartigan-O'Connor, Dennis.

In: Journal of Immunology, Vol. 200, No. 3, 01.02.2018, p. 1124-1132.

Research output: Contribution to journalArticle

Méndez-Lagares, G, Lu, D, Chen, C, Terrault, N, Segal, MR, Khalili, M, Monto, A, Shen, H, Michele Manos, M, Lanier, LL, Ryan, JC, McCune, JM & Hartigan-O'Connor, D 2018, 'Memory t cell proliferation before hepatitis c virus therapy predicts antiviral immune responses and treatment success', Journal of Immunology, vol. 200, no. 3, pp. 1124-1132. https://doi.org/10.4049/jimmunol.1701364
Méndez-Lagares, Gema ; Lu, Ding ; Chen, Connie ; Terrault, Norah ; Segal, Mark R. ; Khalili, Mandana ; Monto, Alexander ; Shen, Hui ; Michele Manos, M. ; Lanier, Lewis L. ; Ryan, James C. ; McCune, Joseph M. ; Hartigan-O'Connor, Dennis. / Memory t cell proliferation before hepatitis c virus therapy predicts antiviral immune responses and treatment success. In: Journal of Immunology. 2018 ; Vol. 200, No. 3. pp. 1124-1132.
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