Increased frequency of CD39⁺CD73⁺ regulatory T cells and Deltex-1 gene expression level in kidney transplant recipients with excellent long-term graft function

Background: The ability of regulatory T cells (Tregs) to limit inflammatory responses has been demonstrated. However, different subpopulations of this cell have varying abilities to suppress alloreactive immune responses. The primary goal of this study was to assess the frequency of CD4⁺FOXP3⁺CD39⁺CD73⁺ Tregs and Deltex-1 gene expression on long-term renal transplant function.

Methods: A total of 49 subjects were divided into 3 groups: (i) the excellent long-term graft function (ELTGF) group, (ii) the chronic graft dysfunction (CGD) group, and (iii) the healthy control (HC) group. Following sample collection, peripheral blood mononuclear cells (PBMCs) were isolated, and the Deltex-1 gene expression level and the frequency of CD4⁺FOXP3⁺CD39⁺CD73⁺ Tregs were evaluated.

Results: The ELTGF group had more CD4⁺FOXP3⁺ Tregs than the CGD group, but the difference was not statistically significant (P = 0.07). However, the frequency of CD4⁺FOXP3⁺CD39⁺CD73⁺ Tregs and the ratio of these cells to total CD4⁺ lymphocytes significantly increased in the ELTGF group than in the CGD group (P = 0.04 and P = 0.02 respectively). In addition, the expression level of the Deltex-1 gene was significantly lower in the CGD group than in the other 2 groups (P = 0.01 and P = 0.04 respectively).

Conclusions: Given the increased frequency of CD4⁺FOXP3⁺CD39⁺CD73⁺ Tregs and the expression level of the Deltex-1 gene in the ELTGF group, it appears that these factors probably improved function and long-term survival of the transplanted organ through the suppression of alloreactive responses and reduction of inflammation. In other words, one of the immunological mechanisms involved in the CGD group may be a deficiency in Tregs.