Exploring the influence of tissue resident leukocytes on transplantation tolerance

Clinical Professor Michaela Lucas, Consultant Clinical Immunologist/Immunopathologist, Sir Charles Gairdner and Perth Children's Hospitals, Western Australia

Organ transplantation is the final treatment option for many end-stage diseases, however it does not provide a lifelong cure. Current immunosuppressive therapy predominantly focuses on the prevention of acute rejection responses due to minor and major tissue mismatches. Primarily due to chronic rejection, which can be compared to premature ageing of transplant organs, long-term survival rates have remained at <50% for the past 20 years. Chronic rejection remains poorly understood, however recently identified ‘tissue-resident’ (TR) leukocytes may play an important role in transplant survival due to their abundance and location in commonly transplanted organs. Furthermore, sterile inflammation is an unavoidable consequence of transplant surgery which contributes to intragraft inflammation and likely chronic rejection. The inflammatory innate response to graft organs remains ill-defined and its better understanding may provide critical insights on how to prolong healthy graft organ function and improve overall wellbeing of transplant recipients. Using orthotopic liver and heterotopic heart transplants in mice, we have characterised donor and recipient leukocytes post-transplantation as well inflammatory responses to the grafts and aligned them with outcome. Different models with various strain combinations allow us to study the immunology behind both rejection and tolerance outcomes.

Clinical Professor Michaela Lucas is a Consultant Clinical Immunologist/Immunopathologist at Sir Charles Gairdner and Perth Children's Hospitals in Western Australia; she is a research group leader at the Harry Perkins Institute, University of Western Australia.  She is currently the President Elect of the Australasian Society of Immunology and Clinical Immunology (ASCIA), Chair of the ASCIA Drug Allergy Committee and is playing a key role in the development of national Australian guidelines concerning the management of drug allergy. Michaela has a strong background in T- cell immunology, notably in describing the role of classical and non-classical T cell responses to the pathogenesis of infections and, most recently, in drug allergy and solid organ transplantation. Since 2014 she heads a basic immunological research laboratory with a focus on inflammation and the role of tissue resident cell populations in transplantation.