The Discipline of Immunology in Trinity Translational Medicine Institute at St. James’s Hospital is currently home to full-time researchers, visitors from collaborating departments, and students doing projects in translational immunology. In close partnership with the Immunology Diagnostic Laboratories at St. James’s Hospital, our research is aimed at finding out how the immune system can protect against or cause disease in humans and how it can be manipulated for the development of novel diagnostics and therapies for a wide range of immunological diseases, from the very common to the vanishingly rare.
Our service has a wide-ranging interest in patient focused research across a range of disorders. In recent years we have participated in international multisite clinical trials in rare disorders. This has included significant contributions to the study of new treatments in ultra-rare disorders such as activated PI3 kinase delta syndrome and an ongoing study of new treatments for C1 esterase inhibitor deficiency.
We have a keen interest in chronic urticaria, contributing to international projects and developing our own research themes examining mast cell progenitors and alterations in coagulation cascades in this unusual disorder.
In collaboration with the Trinity Health Kidney Centre, our diagnostic laboratory has played a key role in the translation of the urinary CD163 to clinical use as a biomarker for glomerulonephritis in the setting of ANCA associated vasculitis. We are partnering with rheumatology colleagues in the examination of risk factors and biomarkers in the setting of polymyalgia rheumatica and giant cell arteritis.
Our diagnostic laboratory played a key role in the evaluation of indices of immunity to COVID-19. Our work provided evidence of immunological factors predictive of severe disease in acute COVID-19 and a timely early assessment of immune parameters in healthcare workers with prolonged COVID-19 sequelae. The diagnostic laboratory team played a key role in the PRECISE longitudinal series of studies of humoral and cellular immunity in COVID 19, including establishing a scalable whole blood COVID-19 interferon gamma release assay. We are building on the skills developed during the pandemic and diversifying our projects to collaborate with neurology colleagues in the examination of EBV responses in the setting of multiple sclerosis.
We contribute to the ESID database in inborn errors of immunity, the rare kidney disease biobank and the CURE – chronic urticaria project. We also collaborate with our intensive care unit colleagues in the setting of drug allergy and are looking forward to international partnerships in this arena.
Our department produces the clinical immunology podcast ‘Immunotea’ downloadable from all major podcast providers.
Prof. Doherty’s group is interested in novel populations of T lymphocytes, known as innate T cells, which appear to be “master regulators” of the immune system, being able to determine the type and strength of an immune response, and which are defective in many infectious and immune-mediated diseases and cancers. Innate T cells include invariant natural killer (iNKT) T cells, mucosal-associated invariant T (MAIT) cells and a number of subsets of gamma/delta (γδ) T cells (Vδ1, Vδ2 and Vδ3 T cells), and they recognize and respond to glycolipids, pyrophosphates, carbohydrates and other metabolites that are produced by microbial pathogens or by host cells responding to pathogen exposure or tumour transformation. We have demonstrated that innate T cells can influence the activation and subsequent responses of other immune cells, including natural killer, dendritic cells, B cells and conventional T cells and have provided in vitro evidence to support their utility for immunotherapy. In collaboration with clinical colleagues at Trinity College Dublin, we have studied various innate T cell populations in patients with viral, bacterial and fungal infections, lung, liver, oesophageal, gastric and blood cancers, autoimmune and inflammatory disease, sepsis and immunodeficiency. We are also investigating how innate and conventional lymphocyte subsets influence recovery from blood cancers post allogeneic stem cell transplantation and CAR-T cell therapy. The results show that particular innate T cells can be manipulated to promote the generation of desirable immune responses for the treatment of disease.
|This cartoon shows the many different outcomes of innate T cell activation by conserved antigens. Conserved components of pathogens or host cells (antigens) bound to the surface of antigen-presenting cells are recognised by “semi-invariant” antigen receptors on innate T cells resulting in rapid and selective activation, polarisation and regulation of a wide variety of adaptive immune responses.|