Freeing Virus-Specific T Cells from their Antigen Burden: Full Recovery or Long-term Disability?
T cell exhaustion is a central mechanism of immune evasion for viruses and malignancies. Despite recent scientific and medical breakthroughs demonstrating that T cell exhaustion can be overcome, important questions remain regarding the specific cellular programs governing T cell exhaustion. It is also unclear to what degree removal of persistent antigen, as the original cause for T cell exhaustion, can lead to recovery of T cell functions and memory formation. Here we utilized the unique new hepatitis C virus (HCV) therapies with direct acting antivirals (DAA) as a highly specific perturbation in a persistent viral infection in humans, as these therapies control and terminate viral replication within days of initiation of therapy. We designed a trial around DAA therapy with sampling of leukapheresis products and liver fine needle aspirates before and after treatment, enabling us to perform comprehensive immune analysis in both the blood and the liver as the site of infection. Our key findings are that virus specific CD8 T cells recover in phenotype, but little in antiviral functions post HCV cure. With regards to HCV-specific CD4 T cells, we find no significant improvement of the response in patients with treatment of chronic infection, but a rescue of these responses if treatment is initiated early after exposure. Overall our results indicate that antigen-specific T cell responses undergo partial recovery after termination of viremia, unlikely to mediate protection from re-infection. The cells might, however, be amenable to additional immunomodulatory interventions targeting remaining molecular road blocks to full functional recovery. Finally, recovery of the CD4 T cell response might be only possible during a much shorter window of opportunity after establishment of persistent viremia.
Date: 21 March 2018, 12:00 (Wednesday, 10th week, Hilary 2018)
Venue: Medawar Building, off South Parks Road OX1 3SY
Venue Details: Level 30 Seminar Room
Speaker: Georg M Lauer (Harvard Medical School)
Organising department: Department of Zoology
Organisers: Thomas Johnson (Department of Zoology), Andrea Kastner (Department of Zoology)
Organiser contact email address: thomas.johnson@tss.ox.ac.uk
Host: Professor Sunetra Gupta (University of Oxford)
Part of: Peter Medawar Building Seminars
Topics: Viruses--Research, T cells, Immune system, Phenotype, Hepatitis C virus
Booking required?: Not required
Cost: FREE
Audience: UK Scientific Community
Editors: Andrea Kastner, Thomas Johnson