Still a few places left for this one day event-Friday, 05 March 2010 08:45 - 17:15
To book your place click here -http://www.regonline.co.uk/regT2010
Leolin Price Lecture Theatre
UCL Institute of Child Health
30 Guilford St
London
WC1N 1EH
United Kingdom
"This meeting will provide an update on phenotypic and functional aspects of regulatory T cells, aiming to inform, educate and entertain. Presentations will be delivered by world-class leaders in their respective fields and a lively discussion will follow each series of talks. Coupled with the pleasant ambience and modern facilities of the venue, this event promises to be one not to be missed" Meeting Chair: Dr Oliver Garden,The Royal Veterinary College, London, UK This meeting has CPD accreditation 8:45 – 9:15 Registration 9:15 – 9:25 Introduction by the Chair: Dr Oliver Garden, The Royal Veterinary College, London, UK Dr Jian-Guo Chai, Imperial College London, UK Regulatory T cells function to dampen pathogenic immune responses and were originally identified by their role in preventing autoimmunity. Tumour antigens are also self-antigens and tumour specific immunity can be compromised by the activity of regulatory T cells. To investigate the influence of the tumour environment on regulatory T cells, we have developed models in which tumour specific or non-specific regulatory T cells are transferred into tumour bearing hosts. Using this approach, we have examined regulatory T cell expansion, the role of tumour derived TGFb, stability of Foxp3 expression, development of inducible regulatory T cells and the impact of vaccination. Professor Michael Ehrenstein, Professor of Experimental Rheumatology, Windeyer Institute, University College London, UK Regulatory T cells (T reg) from patients with RA have defective suppressor function. Following anti-TNF-alpha (infliximab) treatment, Treg from RA patients appear to regain their suppressive function, but only in those individuals who respond to therapy. However, infliximab, rather than restoring the defect in Treg, induces the differentiation of a distinct and potent population of CD62L- Treg from responder T cells. The suppressive capability of these CD62L- Tregs is dependent upon TGF-beta and IL-10, unlike Tregs from healthy individuals which suppressed through cytokine independent mechanisms. Our recent results suggest that defects in CTLA-4 could contribute to abnormal Treg function in RA, and may represent a target for therapy to induce long lasting remission. 10:55 - 11:00 Speakers’ photo 11:00 – 11:20 Mid-morning break and poster viewing 11:20 – 12:05 Induction and function of antigen specific Tr1 cells in human diseasesProfessor Maria Grazia Roncarolo, San Raffaele Telethon Institutefor Gene Therapy (HSR-TIGET), Italy Adaptive IL-10-producing regulatory T (Tr1) cells develop in the periphery upon chronic antigen-stimulation in the presence of IL-10 secreted by tolerogenic APC. Tr1 cells are required for tolerance induction to self- and non-self antigens. Indeed high percentages of allo-specific Tr1 cells, with regulatory functions, are present in peripheral blood of patients who developed persistent chimerism after allogeneic hematopoietic stem cell transplantation. We recently identified a population of human tolerogenic DC, called DC-10, present in vivo and inducible in vitro, that are powerful inducers of antigen-specific Tr1 cells. DC-10 can be used to generate ex vivo Tr1 cells for cell therapy to modulate pathological immune-responses to different antigens. 12:05- 12:20 Cell Processing tools for preclinical and clinical studies in immunotherapy and regenerative medicine Dr Catherine Barjot , CellGenix, Germany CellGenix is a German biopharmaceutical company that develops, produces and markets research and GMP grade cell processing tools for cell therapy. CellGenix was founded in 1994 as a spin-off of the University Medical Center of Freiburg. Initially focused on immunotherapy , CellGenix has developed serum free culture media and cytokines for culture and expansion of human T cells, NK, Dentritic Cells and Hematopoietic Stem Cells. The CellGenix serum free media and a lot of the CellGenix cytokines such as IL-15 and IL-7 are available as GMP grade products. Sima HiraniNHS Blood and Transplant, Colindale, UK Melissa Robbin, The Royal Veterinary College, London, UK Tregs have been described in numerous species such as humans, mice, cats, dogs and pigs. We have recently identified appropriate reagents to identify Tregs in horses using CD4 and FOXP3 as markers. We observed an increase in FOXP3 expression after stimulation, and a decrease in expression in aged individuals within CD4+ lymphocytes. We further attempted to phenotypically characterise these Tregs by analysing cytokine secretion after stimulation. Further research aims to demonstrate suppressive function of these equine Tregs using suitable antibodies that detect equine CD25, which will aid in highlighting species-specific difference that exist within Tregs. Dr Emily Staples, Nottingham Digestive Diseases Centre, Nottingham, UK. 14: 00 - 15:00 Keynote address: Regulatory T cell control of pathogenic and effector T cells - implications for cancer and autoimmunity Professor Kingston Mills, Professor of Experimental Immunology and Head School of Biochemistry and Immunology, Trinity College Dublin IL-17-producing CD4+ T cells (Th17 cells) play a pathogenic role in organ specific autoimmune diseases and function with Th1 cells to mediate protective immunity to pathogens. The differentiation of Th17 cells from naïve T cells is promoted by IL-6, IL-21, IL-1b and IL-23. Furthermore, IL-1a or IL-1b in synergy with IL-23 can promote IL-17 secretion from memory T cells and gd T cells. Regulatory T (Treg) cells can suppress pathogenic T cells directed against self-antigens and thereby prevent autoimmunity, but also limit collateral damage during immune responses to infection. We are examining the balance between Th17 and Treg cells, and the consequences of its disruption, in mouse models of infection, hitherto considered to be dominated by Th1 or Th2 cells. This information is being used to design approaches for selective activation of Treg cells, which can inhibit Th17 cells that mediated autoimmunity, or for selective inhibition of Treg cells, to enhance effector Th1 cells and thereby develop more effective immunotherapeutics and vaccines against infection or cancer. 15: 30-16:15 Effector function and regulation in bacterial sepsis Professor Daniel Altmann, Professor of Immunology/Deputy Head of Department in the Department of Infectious Diseases and Immunity, Imperial College London, UK Group A streptococcal (GAS) infections can manifest as a range of presentations from sore throat to scarlet fever, rheumatic fever, septic or toxic shock and necrotizing fasciitis. Many GAS genomes harbour genes encoding superantigens, accounting for some aspects of the immune/inflammatory phenotypes associated with infection. For this reason there has been considerable focus, both in humans and mouse models, on analysing the balance between microbial and immunological contributions to pathogenesis. Gram-positive sepsis is a highly pertinent setting for questions of immunopathology versus host defense, constituting a significant clinical problem with respect to high mortality and a paucity of effective immune-therapeutics: mortality in septic shock is in the 40-70% range. As one might expect for a pathogen capable of inducing shock through an excessive inflammatory response, the acute response to infection encompasses increases in both effector T cell and Treg populations. Transcription factors associated with Tregs as well as Th1, Th2 and Th17 profiles increase strongly with the first hours after infection. Particularly important in this initial response seems to be the IL-17 response derived predominantly from gamma delta T cells. 16: 15-17:00 Barriers and challenges in regulatory T cell therapy for solid organ transplantation Professor Giovanna Lombardi, Division of Medicine, King’s College London, UK Naturally arising CD4+CD25+ regulatory T cells play a pivotal role in the prevention of autoimmunity. Strategies are under development to establish ways of expanding Tregs in vitro for clinical use to achieve tolerance in autoimmunity and transplantation. In the last few years, we have built a platform of data in murine models which support the hypothesis that Tregs are very efficient in inducing allograft survival. However, we and others have shown recently that human Tregs under inflammatory conditions are prone to conversion to proinflammatory Th17 cells, which have been shown to be key effector cells in autoimmune responses and in graft rejection. In this study we have investigated the mechanisms of human Treg to Th17 conversion. We have shown that the major cytokine involved in the conversion of human Tregs to Th17 in vitro is IL-1 and that this effect is mediated by a shift from functional activation of STAT5 to STAT3. This conversion was critically dependent on STAT3 as Tregs from human patients with dominant-negative mutations in STAT3 did not produce IL-17 in response to IL-1. Despite the role of IL-6 in activating STAT3, this cytokine did not convert Tregs to Th17. Analysis of SOCS proteins demonstrate that IL-1 but not IL-6 could promote a permissive enviroment for SOCS protein. Our data provide mechanistic insight into the actions of IL-1 induction of Treg to Th17 conversion. Different strategies are now under investigation to identify molecular difference between Tregs pre- and post-conversion, to prevent their subversion. The success of these strategies will influence the design of the first trial in which Tregs will be used in organ transplantation, where inflammation is present by avoiding the risk of conversion to IL-17 producing cells. 17:00-17:15 Chairman’s summing up
Abstract submissions are invited from PhD students and junior post docs (within three years of PhD graduation), from which several will be chosen to be presented as posters and three to be presented orally; presenters of all of the selected abstracts will be reimbursed their registration fee. Of the three best abstracts chosen for oral presentation, the audience will vote on the best overall talk, for which the presenter will be awarded a prize of a year’s subscription to Nature Reviews ImmunologyorMucosal Immunology (www.nature.com/mi) at the conclusion of the day. There will also be a runners up prize.
9:25 – 10:10 The influence of the tumour environment on regulatory T cells
10:10 – 10:55 Harnessing regulatory T cells for therapy in rheumatoid arthritis
12:20 – 12:30 Characterisation of umbilical cord blood derived regulatory T cells
12:30 – 12;40 Evidence for natural regulatory T cells in the horse and their decline in aged individuals
12:40 – 12:50 Helicobacter pylori-induced protection from allergy is associated with peripheral blood regulatory T cells
12:50 -14: 00 Lunch and Networking
15:00-15:30: Afternoon break and last poster viewing
