Gamma-Chain Receptor Cytokines & PD-1 Manipulation to Restore HCV-Specific CD8 + T Cell Response during Chronic Hepatitis C
Authors
Peña Asensio, JuliaIdentifiers
Permanent link (URI): http://hdl.handle.net/10017/50987DOI: 10.3390/cells10030538
ISSN: 2073-4409
Date
2021-05-03Funders
MINECO
Instituto de Salud Carlos III
European Commission
Gilead Fellowship Programme
European Regional Development Fund (ERDF)
Bibliographic citation
Cells, 2021, v. 10, n. 3, p. 538-
Keywords
CD8+ T cell response
Hepatitis C virus
IL-15
IL-2
IL-21
IL-7
PD-1
PD-L1
Exhaustion
Immune checkpoints
Gamma-chain cytokines
Project
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/ PI19%2F00206/ES/
info:eu-repo/grantAgreement/Gilead Sciences/ Gilead Fellowship Program in HIV & Hepatitis/ GLD14%2F00217 (JRL)/ES/
info:eu-repo/grantAgreement/Gilead Sciences/ Gilead Fellowship Program in HIV & Hepatitis/ GLD16%2F00014 (JRL)/ES/
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/publishedVersion
Rights
© 2021 by the authors. Licensee MDPI
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Access rights
info:eu-repo/semantics/openAccess
Abstract
Hepatitis C virus (HCV)-specific CD8+ T cell response is essential in natural HCV infection control, but it becomes exhausted during persistent infection. Nowadays, chronic HCV infection can be resolved by direct acting anti-viral treatment, but there are still some non-responders that could benefit from CD8+ T cell response restoration. To become fully reactive, T cell needs the complete release of T cell receptor (TCR) signalling but, during exhaustion this is blocked by the PD-1 effect on CD28 triggering. The T cell pool sensitive to PD-1 modulation is the progenitor subset but not the terminally differentiated effector population. Nevertheless, the blockade of PD-1/PD-L1 checkpoint cannot be always enough to restore this pool. This is due to the HCV ability to impair other co-stimulatory mechanisms and metabolic pathways and to induce a pro-apoptotic state besides the TCR signalling impairment. In this sense, gamma-chain receptor cytokines involved in memory generation and maintenance, such as low-level IL-2, IL-7, IL-15, and IL-21, might carry out a positive effect on metabolic reprogramming, apoptosis blockade and restoration of co-stimulatory signalling. This review sheds light on the role of combinatory immunotherapeutic strategies to restore a reactive anti-HCV T cell response based on the mixture of PD-1 blocking plus IL-2/IL-7/IL-15/IL-21 treatment.
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gamma_peña_CELLS_2021.pdf | 8.086Mb |
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