Editorial
Regulatory T cells: From bench to bedside

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Abstract

Regulatory T cells (Tregs) are subsets of T cells that are specifically dedicated to controlling immune responses. It has been established that Tregs play a key role in regulating autoimmune disease, allergy, cancer, infectious disease, and in the induction of transplantation tolerance. The latest progress in the development, function, mechanism of action, and homeostasis of regulatory T cells, and their translation to the clinic were presented at the International Conference on Regulatory T Cells and Clinical Application in Human Diseases in Beijing on 25–27 October 2008 (China Tregs 2008). In this Special Issue of International Immunopharmacology, several papers submitted to the China Tregs 2008 will highlight some of the recent advances in the biology of regulatory T cells and current strategies to translate regulatory T cells into the clinic.

Introduction

In the past decade several subsets of regulatory T cells (Tregs) have been described in both human and rodents [1]. Among them are naturally occurring CD4+CD25+ Tregs. The importance of this population of Tregs in the control of autoimmunity was first demonstrated by Sakaguchi et al. in 1995 [2]. They showed that the spontaneous development of autoimmune disease in thymectomised neonate mice could be prevented by the adoptive transfer of CD4+CD25+ T cells from normal mice [2]. Subsequent studies have showed that transcript factor Foxp3 gene appears to play a key role in the ontogeny of CD4+CD25+ Tregs [3], [4]. Mutation of Foxp3 gene in human causes the IPEX syndrome [5]. Now it is clear that Tregs are the key regulators for the control of all immune responses including autoimmunity, tumor immunity, infection, allergic reaction and transplantation tolerance, and their translation to the clinic would lead to cure many forms of human diseases [1]. In October 2008, an international conference held in Beijing, China (China Tregs 2008) was dedicated entirely to the latest progress in the biology of Tregs including their development, function, mechanism of action, and homeostasis, and their clinical application in human diseases [6].

Section snippets

Foxp3 biochemistry and the development, homeostasis, stability and function of Tregs

Foxp3 is key regulator for Treg function and homeostasis. In this Special Issue of China Tregs 2008, Zhou et al. from University of Pennsylvania (USA) summarized their recent data on the structure and the ensemble of Foxp3 transcription factor. The crystal structure of Foxp3 revealed that Foxp3 oligomerization domain as an anti-parallel coiled coil with a potential to mediate high-order homo or hetero oligomerization. The homo-oligomerization of Foxp3 would promote proper organization of the

Treg therapy in autoimmunity, cancer, and transplantation tolerance

Naïve CD4+ T cells are able to differentiate into either Tregs (induced Tregs: iTregs) or IL-17 producing effector Th17 cells under immunosuppressive milieu of TGF-b or inflammatory condition of TGF-b and IL-6. In this Special Issue of China Tregs 2008, Huter et al. from National Institutes of Health (NIH, USA) demonstrated that antigen-specific iTregs were more potent than polyclonal iTregs in inhibiting Th17-mediated autoimmune gastritis, and polyclonal nTreg had no effect. Their data are in

Preclinical studies of Tregs in primates and in patients

It has been showed that CD4+CD25+ Tregs have impaired suppressive function in multiple sclerosis (MS) patients [12]. In this issue, Ma et al. from University of Montréal (Canada) studied the number and function of Tregs in a mimic model of human MS in Cynomolgus Monkeys. They found that dysfunction of CD4+CD25+ Tregs and IL-10 producing type 1 regulatory T cells (Tr1 cells) contributed to the pathogenesis of the disease, and adoptive transfer of Tregs would be a clinical applicable strategy to

Conclusion

At China Tregs 2008, more than 60 of world's most renowned Treg experts gave the sought-after plenary presentations on the biology of Tregs and its clinical application in human diseases. Further 40 plenary oral presentations and 200 abstracts were also presented at the conference. The presentations of world's most senior speakers have been featured in the recently published textbook “Regulatory T cells and Clinical Application” (Springer, New York), edited by Shuiping Jiang [1], and in the

References (12)

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