Regulatory T Cells In Transplantation: Does Extracellular Adenosine Triphosphate Metabolism Through Cd39 Play A Crucial Role?

Abstract

Despite Tremendous Improvements In Short-Term Renal Allograft Survival, Many Patients Still Have Chronic Rejection Or Side Effects Of Nonspecific Immunosuppression. The Discovery Of Foxp3+ Regulatory T Cells (Tregs) Has Revolutionized The Concepts In Immunoregulation And Offers Perspectives For Overcoming Rejection. Recently, A Subset Of Foxp3+Cd39+ Effector/Memory-Like Tregs (Trem) Was Identified. The Role Of Cd39+ Tregs In Immunoregulation Is Supported By The Occurrence Of Alopecia Areata And Experimental Autoimmune Encephalomyelitis In Cd39-Deficient Mice And By The Failure Of Cd39- Tregs To Suppress Contact Hypersensitivity. In Humans, Cd39 Polymorphisms Have Been Associated With Diabetes And Nephropathy, And Multiple Sclerosis Patients Have Reduced Numbers Of Blood Cd39+ Tregs. Preliminary Experiments In A Murine Transplantation Model Showed That Cd39+ Tregs Can Determine Allograft Outcome. Cd39 Degrades The Extracellular Adenosine Triphosphate (Atp) Released During Tissue Injury, Which Otherwise Would Trigger Inflammation. Currently, Our Groups Are Assessing The Role Of Cd39+ Tregs And Extracellular Atp Metabolism In Clinical Transplantation And Whether Tolerogenic Treg Profiles Possess Immunopredictive Value, Envisioning The Development Of Clinical Trials Using Cd39+ Treg-Based Vaccination For Autoimmunity Or Transplantation. This Is A Comprehensive Review On The Fundamentals Of Treg Biology, The Potential Role Of Atp Metabolism In Immunoregulation, And The Potential Use Of Treg-Based Immunotherapy In Transplantation. © 2010 Elsevier Inc.