Regulatory T cells in transplantation - from preclinical models to clinical study

Kathryn Wood

doi:10.1186/ar3408

Abstract

After exposure to alloantigen in vivo and in vitro, alloantigen reactive immunoregulatory activity is enriched in a population of CD4+ T cells that express high levels of CD25, the α chain of the interleukin-2 receptor, and the transcription factor FOXP3. In vivo, common mechanisms underpin the activity of CD25+CD4+ Treg in adult hosts. We identified a unique role for IFNγ in the functional activity of CD25+CD4+ alloantigen reactive Treg during the development of operational tolerance to donor alloantigens in vivo that is consistent with observations showing that tolerance to alloantigens cannot be induced in the absence of IFNγ [1]. In order to provide proof of concept data for translation of findings in preclinical models to the bedside, we have demonstrated that human regulatory T cells expanded ex vivo can protect human allografts (skin and vessels) from rejection [2,3]. The identification and characterisation of Treg that can control immune responsiveness to alloantigens has opened up exciting opportunities for new therapies in transplantation.

Highlights

I1 Kitasato symposium 2011: translational prospects for cytokines Gerd R Burmester1, Peter E Lipsky2, Thomas Dörner2*, the Kitasato Meeting Faculty 1Dept
O2 Inducing a tolerogenic microenvironment within tissues Stephen P Cobbold Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK E-mail: stephen.cobbold@path.ox.ac.uk Arthritis Research & Therapy 2011, 13(Suppl 2):O2
The maintenance of tolerance to both self tissues foreign organ grafts depends on the activity of foxp3+ regulatory T cells (Treg)

Summary

INTRODUCTION

I1 Kitasato symposium 2011: translational prospects for cytokines Gerd R Burmester, Peter E Lipsky, Thomas Dörner2*, the Kitasato Meeting Faculty 1Dept. After successful meetings in 2009 and 2010, an international faculty of largely immunologists and rheumatologists will gather in Potsdam on September 22nd and 23rd, 2011 to discuss the impact of cytokines in health and their contributions to autoimmunity in a symposium named after Shibasaburo Kitasato (1853 - 1931), who worked in Berlin between 1885 and 1892 During this rather short time, he together with Emil von Behring discovered the causative pathogens of tetanus and diphtheria and contributed substantially to our basic understanding of the interaction of the immune system and invading pathogenic microorganisms In keeping with the tradition of Kitasato, a major theme of the symposium will be the translation of basic science principles into understanding human disease. The collection of the individual contributions is summarized in the following abstract supplement

KEYNOTE LECTURE PRESENTATION

Abstract not submitted at time of publication

Background