Regulatory T cells (Tregs) are essential actors in the control of self-tolerance and exacerbated inflammation. In experimental transplantation Tregs are critical to achieve alloantigen tolerance and improve graft survival. To date clinical relevance for the role of Tregs human kidney transplantation came from association studies demonstrated that elevated circulating and graft-resident Tregs are associated with better outcomes.

Operational tolerant patients are a subgroup of transplant recipients who tolerate their graft without the use of suppressive therapy. Previous studies demonstrated that underlying mechanisms promoting graft tolerance could rely on a specific regulatory B and T cells responses. Recently published observations from our group demonstrated that Tregs from tolerant patients exhibit a more activated/memory profile as witnessed by a higher FOXP3 demethylation, higher suppressive function and higher expression of CD39 a key molecule in the regulatory function of Tregs (Braza et al., 2015, JASN).

Recently we confirmed our previous observation in a large cohort of tolerant patients and demonstrated that expression of CD39 was slightly increase in circulating memory Tregs when compared to stable recipients. In the light of their first results we are currently exploring and comparing the ability of TOL mTregs to degrade the pro-inflammatory mediator ATP into AMP and adenosine via the CD39 / CD73 pathway and in what extend these cells can suppress inflammation in vitro.

Additionally, and based on recent advances in Tregs phenotyping (Miyara at al., 2015, PNAS), we found that tolerant patients have increased frequency of CD15s⁺ antigen-experienced mTregs suggesting an overall activation of these cells in vivo in the tolerant group. To get more insights into the molecular profile of mTregs in operational tolerance we sorted these cells from the blood of helathy volunteers, TOL, STA and RC to perform RNA-Seq analysis.

Altogether these data will demonstrate that operational tolerance presumably involve active mechanisms in which immune regulation by suppressive regulatory T cells allows to maintain a physiological regulatory/effector T-cells functions balance. One of the main mechanisms could be the extracellular ATP degradation through the CD39/CD73 pathway.

CITATION INFORMATION: Durand M, Braza F, Degauque N, Dubois F, Chesneau M, Guérif P, Giral M, Brouard S. Memory Regulatory T Cell: A Potential Actor in Immunological Operational Tolerance in Kidney-Transplant Patients via the ATP Degradation into Adenosine. Am J Transplant. 2016;16 (suppl 3).

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