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Epithelial molecules shaping immunosurveillance by local T cells

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Air date: Wednesday, May 10, 2017, 4:15:00 PM
Time displayed is Eastern Time, Washington DC Local
Views: Total views: 317, (39 Live, 278 On-demand)
Category: Immunology
Runtime: 01:02:47
Description: Immunology Interest Group Seminar Series

The thesis of conventional immunology is centralized control whereby responses to infection within tissues are decided within lymph nodes, from which effector T lymphocytes are dispatched to quell regional disturbances. But this cannot explain the observation that many tissues at steady state are T cell-rich. Do such cells simply provide responses to infection or do they provide more generalized means to sustain tissue integrity and organ function? Likewise, how are such cells able to respond to acute stress but not drive constitutive tissue inflammation? And, how do immune cell–tissue interactions relate to organ physiology? To approach these questions, we have employed molecular genetics to identify key receptor-ligand axes that tissues use to communicate with their local T cell compartments at rest, upon infection and upon non-infectious dysregulation. These axes show how epithelial cells in the thymus and at body surfaces selectively educate specific T cell subtypes, thereby establishing the organ-specific composition and activities of local T cells. The molecules mediating epithelial control over tissue T cell immunity are implicated in inflammatory disease and cancer and offer hope for highly localized clinical regulation.

Adrian Hayday was trained in biochemistry at Cambridge, and obtained a PhD in molecular virology from London University. He began studying immunology in 1982 at MIT, where he and his colleagues first described the wholly unanticipated T cell receptor gamma chain genes. Since then Professor Hayday has used many parameters to establish that gamma delta T cells are clearly distinct from conventional T cells. Those parameters include the cells’ responses to different products of a novel gene family expressed at body surfaces, that Professor Hayday and his colleagues identified. He showed that this unique biology allows gamma-delta T cells to make rapid responses to tissue dysreguation, rather than to specific pathogens, and thereby to monitor tissue integrity. This may explain Professor Hayday’s observation that gamma delta T cell deficiency is associated with a profound susceptibility to skin carcinogens, findings that were instrumental in promoting his and others’ ongoing interest in the cells’ clinical application. In other clinical activities, he directed a team describing the human immune response to vaccination; and he described the unique properties of human autoantibodies harboured by individuals with deficiencies in T cell tolerance. Additionally, he is the lead-investigator of a Wellcome Trust-supported, multi-centre, high-throughput phenotyping screen identifying novel genetic regulators of the immune system.

Professor Hayday has authored over 200 papers, of which he is first, last, or corresponding author on over 120, and of which 150 are original research contributions. He has received many awards, including the William Clyde deVane Medal, Yale College’s highest honour for scholarship and teaching, an honorary fellowship of King’s College London, and the King’s College Business Award, 2008. He was elected to lead the British Society of Immunology (2005-09) and has organized many scientific meetings including the 2014 Gordon Conference in Immunochemistry and Immunobiology, and the scientific programme for the 2012 European Congress of Immunology. He is an elected fellow of the Academy of Medical Sciences and of the Royal Society.

He has formally advised many institutions including Institut Pasteur; the Max Planck Institute; Kyoto University, and the Wellcome Trust, and Cancer Research UK, whose respective funding committees he chaired for three years. He has participated in many aspects of the biotech/pharmaceutical sector, including membership of the MedImmune SAB, and was a co-founder of ImmunoQure AG before co-founding GammaDelta Therapeutics in 2016.
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Author: Adrian Clive Hayday, FMedSci FRS, Glendinning Professor and Chair, Department of Immunobiology, King's College London, Group leader at the Francis Crick Institute, UK
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CIT Live ID: 18522
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