Gavin Pettigrew, United Kingdom

Reader
Department of Surgery
University of Cambridge

I am a reader in clinical and experimental transplantation within the department, having received a clinician scientist award from the Health Foundation in 2003. My research interests focus on the basic science of transplant rejection, with particular emphasis on how the specialised immune cells of the recipient – the T and B lymphocytes – coordinate in the development of antibody. We are increasingly aware that, after transplantation, the development of antibody directed against the transplant is associated with early failure of the transplant. Hence, a better understanding of how antibody develops will allow us to develop new strategies that aim to prevent the development of antibody, and in doing so, prolong transplant survival. Over the last few years, research from the group has shown that the ‘indirect’ T cell allorecognition is crucial in the provision of help for alloantibody production, and that germinal centre alloantibody responses are critically dependent upon help from allospecific ‘T Follicular Helper’ cells that recognise self-restricted processed allo-peptide. Our most recent research suggests that targeting this specialised T cell subset may be an attractive approach to combating chronic antibody mediated rejection. Finally, our research has highlighted that the T cell allorecognition pathways active at various times after transplantation may vary considerably, as will the precise alloantigenic focus of these responses, and has detailed a novel mechanism by which passenger donor lymphocytes within a transplant may augment the recipient’s alloimmune response. ‘ As a transplant surgeon, I also have a research interest in promoting and expanding the UK donor pool. Over the last decade, deceased donation in the UK has changed dramatically, because of the increased use of ‘donation after circulatory death’ (DCD) donors. These are donors who do not fulfil brain-stem death criteria, but whose survival prospects are futile due to catastrophic brain injury. This expansion in DCD activity has approximately doubled the numbers of UK donors annually, and currently, almost half of deceased donors in the UK are from DCD donors. This is a very different situation than occurs in the States and other European countries, and I am extremely proud that the work we have performed in Cambridge has been central to the expanded DCD UK transplant activity. Generally, retrieval teams wait one hour before abandoning donation after withdrawing life supporting treatment (WLST) in a potential DCD donor, but our research has shown that that numbers of DCD kidney transplants can be substantially increased by waiting longer from WLST, and that this does not prejudice transplant outcome (Reid et al, AJT 2011). This has informed national practice – organ retrieval teams in the UK now all wait a standard three hours from WLST. Our research has also shown that kidneys from elderly DCD donors can be used effectively and safely. To do so in Cambridge, we have adopted a strategy of performing pre-implantation biopsy analysis of kidneys from elderly DCD donors. These biopsies are analysed urgently and the results of the analysis used to inform the decision about whether to implant the kidneys as single, or dual transplants (two kidneys into the one recipient), or to discard. I am currently leading an NIHR-funded National Trial aimed at evaluating how the introduction of a National Histopathology Service impacts upon the number, and outcomes, of deceased kidney transplants performed in the UK (see http://www.pithia.org.uk/).



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