Gamma-Chain Receptor Cytokines & PD-1 Manipulation to Restore HCV-Specific CD8+ T Cell Response during Chronic Hepatitis C

Cells

Joaquín Miquel¹  Julia Peña-Asensio¹  Eduardo Sanz-de-Villalobos¹  Henar Calvo¹  Juan-Ramón Larrubia¹  Miguel Torralba² 

[1] Translational Hepatology Unit, Guadalajara University Hospital, E-19002 Guadalajara, Spain;Translational Hepatology Unit, Section of Gastroenterology & Hepatology, Guadalajara University Hospital, E-19002 Guadalajara, Spain;

关键词: Hepatitis C virus;    CD8⁺ T cell response;    exhaustion;    immune checkpoints;    γ-chain cytokines;    PD-1;   

DOI  :  10.3390/cells10030538

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown