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Review
. 2010 Apr;24(2):52-66.
doi: 10.1016/j.trre.2010.01.002. Epub 2010 Feb 11.

Regulatory T cells in transplantation: does extracellular adenosine triphosphate metabolism through CD39 play a crucial role?

Francisco Salcido-Ochoa  1 , Julia Tsang, Paul Tam, Kirsten Falk, Olaf Rotzschke
Affiliations
Review

Regulatory T cells in transplantation: does extracellular adenosine triphosphate metabolism through CD39 play a crucial role?

Francisco Salcido-Ochoa et al. Transplant Rev (Orlando). 2010 Apr.

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 (T(REM)) 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.

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