Sidney Truelove Professor of Gastroenterology
Infectious diseases such as HIV, hepatitis B and C, affect hundreds of millions of people worldwide. Our group works on the immune response to these infections, focusing on both the host and the pathogen. As there is currently no vaccine to prevent hepatitis C infection, many of our projects have addressed aspects of chronic hepatitis C virus (HCV) infection and vaccine responses. In addition, our group also looks at a range of viruses and bacteria. Overall our main contributions to date have been to define mechanisms of viral persistence, including: T cell escape, antagonism, original antigen sin, integration of non-retroviral RNA viruses; to define the key features of successful immune responses against HCV, leading to trials of a T cell vaccine; and to define the distinctive CD161+ T cell population, which dominates in the human liver.
We are currently working on three main strands of research:
- CD161++/MAIT cell biology. These lymphocytes, which are abundant in human blood and highly enriched in the liver, have the capacity to respond to both bacterial and inflammatory signals. We are trying to understand their in vivo role in host defence and immunopathology, through the analysis of patients and in vitro studies of function and activation.
- HCV immune defence. In collaboration with the groups of Ellie Barnes and Adrian Hill, we are involved in vaccine studies using adenoviral vectors to track vaccine-induced cells and analyse their capacity to recognise viral variants. Upcoming studies include an analysis of host responses in relation to novel drug therapies and the use of new viral sequencing approaches to define the impact of host immunity.
- Memory inflation. Some persistent virus infections induce a striking host response, which we have termed memory "inflation"; this includes the generation of very large functional T cell populations, which can increase with time. While this was first noted in cytomegalovirus infections, we have found a similar profile of cells after adenoviral vector vaccination. Our group is working to define the qualities of these induced cells, and the critical factors that drive memory inflation.
A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice.
Hackstein C-P. et al, (2022), Nature communications, 13
MR1: An unconventional twist in the tail.
Phalora P. and Klenerman P., (2022), The Journal of cell biology, 221
Combination therapy of infliximab and thiopurines, but not monotherapy with infliximab or vedolizumab, is associated with attenuated IgA and neutralisation responses to SARS-CoV-2 in inflammatory bowel disease.
Wellens J. et al, (2022), Gut, 71, 1919 - 1922
Correction to: MAIT cells in liver inflammation and fibrosis.
Mehta H. et al, (2022), Seminars in immunopathology
Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses
McNaughton AL. et al, (2022), JCI Insight, 7