Treatment of Graft-versus-Host Disease with Naturally Occurring T Regulatory Cells
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REVIEW ARTICLE
Treatment of Graft-versus-Host Disease with Naturally Occurring T Regulatory Cells Piotr Trzonkowski • Anna Dukat-Mazurek • Maria Bieniaszewska • Natalia Marek-Trzonkowska • Anita Dobyszuk • Jolanta Jus´cin´ska • Magdalena Dutka • Jolanta Mys´liwska • Andrzej Hellmann
Ó The Author(s) 2013. This article is published with open access at Springerlink.com
Abstract A significant body of evidence suggests that treatment with naturally occurring CD4?CD25? T regulatory cells (Tregs) is an appropriate therapy for graftversus-host disease (GvHD). GvHD is a major complication of bone marrow transplantation in which the transplanted immune system recognizes recipient tissues as a non-self and destroys them. In many cases, this condition significantly deteriorates the quality of life of the affected patients. It is also one of the most important causes of death after bone marrow transplantation. Tregs constitute a population responsible for dominant tolerance to self-tissues in the immune system. These cells prevent autoimmune and allergic reactions and decrease the risk of rejection of allotransplants. For these reasons, Tregs are considered as a cellular drug in GvHD. The results of the first clinical trials with these cells are already available. In
P. Trzonkowski (&) A. Dukat-Mazurek A. Dobyszuk Department of Clinical Immunology and Transplantology, Medical University of Gdan´sk, Ul. De˛binki 1, 80-211 Gdan´sk, Poland e-mail: [email protected] M. Bieniaszewska M. Dutka A. Hellmann Department of Hematology and Transplantology, Medical University of Gdan´sk, Gdan´sk, Poland N. Marek-Trzonkowska Department of Family Medicine, Medical University of Gdan´sk, Gdan´sk, Poland J. Jus´cin´ska Regional Center of Blood Donation and Treatment, Gdan´sk, Poland J. Mys´liwska Department of Immunology, Medical University of Gdan´sk, Gdan´sk, Poland
this review we present important experimental facts which led to the clinical use of Tregs. We then critically evaluate specific requirements for Treg therapy in GvHD and therapies with Tregs currently under clinical investigation, including our experience and future perspectives on this kind of cellular treatment.
1 Graft-versus-Host Disease (GvHD) Graft-versus-host disease (GvHD) is a complication of allogeneic hematopoietic stem cell transplantation, in which donor immune cells recognize and attack host tissues. It may occur within the first 100 days after allotransplantation as acute GvHD. Acute GvHD manifests as inflammatory lesions in a single or many locations, the most common of which are skin, gut, and liver. The progression of acute GvHD may be very rapid and the disease can be fatal within days or weeks. The onset of GvHD beyond 100 days is classified as chronic. There are some common features of the acute and chronic forms of GvHD but the majority of the symptomatology and pathogenesis are different. Chronic GvHD resembles autoimmune systemic diseases with a long progression, such as lupus or scleroderma. The classical paradigm assumes that there are se
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