Evaluation of CD4+ CD25+/- CD39+ T-cell populations in peripheral blood of patients following kidney transplantation and during acute allograft rejection

Abstract

Aim: Regulatory T cells (Treg) are important in mediating immune tolerance and outcomes of allotransplantation. CD4⁺ CD25⁺ CD39⁺ co-expression identifies memory Treg; CD4⁺ CD25^- CD39⁺ memory T effectors. We sought to determine CD4⁺ CD25^+/- CD39⁺ expression from the peripheral blood of patients with end stage renal failure, following transplantation and during episodes of acute cellular rejection.

Methods: CD4⁺ T cells were isolated from peripheral blood leucocytes and analysed for CD25 and CD39 expression by flow cytometry. Treg suppressive function was measured by suppression of autologous effector T-cell proliferation by Treg in co-culture.

Results: CD4⁺ CD25^+/- CD39⁺ T-cell subsets were tracked longitudinally in the peripheral blood of 17 patients following renal transplantation. Patients with acute T-cell-mediated rejection diagnosed on biopsy had reduced CD4⁺ CD25⁺ CD39⁺ mTreg (P < 0.05) and CD4⁺ CD25^- CD39⁺ mTeff (P < 0.01) cells compared with non-rejecting patients. CD4⁺ CD25⁺ CD39⁺ mTreg (P < 0.05) and CD4⁺ CD25^- CD39⁺ mTeff (P = 0.057) were reduced in long-term transplant patients (>1 year) compared with non-immunosuppressed controls. Interestingly, remaining CD4⁺ CD25⁺ CD39⁺ mTreg in the stable transplant patients displayed more potent suppressive capacity compared with non-immunosuppressed controls (83.2% ± 3.1% vs 45.7% ± 8.0%, nTeff:Treg ratio 8:1, P < 0.01).

Conclusion: CD4⁺ CD25⁺ CD39⁺ mTreg and CD4⁺ CD25^- CD39⁺ mTeff in peripheral blood can be tracked in renal transplant patients. Acute cellular rejection was accompanied by reduced mTreg and mTeff. Determining changes in these T-cell subsets may help to identify patients with, or at high risk of, renal allograft rejection.

Keywords: CD39; Treg; acute cellular rejection; kidney; renal transplantation.