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Kidney Week

Abstract: PO2188

The Balance Between Memory and Regulatory Cell Populations in Kidney Transplant Recipients with Operational Tolerance

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Speer, Claudius, University Heidelberg, Heidelberg, Germany
  • Schaier, Matthias, University Heidelberg, Heidelberg, Germany
  • Zeier, Martin G., University Heidelberg, Heidelberg, Germany
  • Morath, Christian, University Heidelberg, Heidelberg, Germany
  • Süsal, Caner, University Heidelberg, Heidelberg, Germany
Background

Donor-reactive memory cells represent a barrier to long-term kidney graft survival. A better understanding of regulatory mechanisms that counterbalance alloreactive memory responses may help to identify patients with operational tolerance.

Methods

The prospective, bicentric BALANCE study investigated the equilibrium between memory T cell subsets and regulatory T or B cells (Tregs, Bregs) in peripheral blood of kidney transplant recipients with operational tolerance (N=8), chronic rejection (N=8), and different immunosuppressive treatment regimens (N=81). Patients on hemodialysis and healthy individuals served as controls (N=50). In addition, the expression of Treg- and Breg-associated molecule genes was analyzed.

Results

Patients with chronic rejection showed a disrupted memory T cell composition with a significantly increased frequency of circulating CD8+ terminally differentiated effector memory (TEMRA) T cells than in patients with operational tolerance, patients on hemodialysis, or healthy controls (P<0.001). Compared to all other transplant recipients, the lowest ratios between CD8+ TEMRA and naïve or effector T cells and the highest frequency of Tregs and transitional Bregs were found in operationally tolerant patients (for all P=0.001). Consequently, operationally tolerant patients showed, as compared to all other transplant recipients with different immunosuppressive regiments, the lowest ratios between CD8+ TEMRA T cells and Tregs or Bregs (for both P<0.001). A specific peripheral blood transcription pattern was found in operationally tolerant patients with an increased expression of Breg- and Treg-associated genes CD22 and FoxP3 and a decreased FcγRIIA/FcγRIIB transcript ratio (for all P<0.001, as compared to all other transplant recipients).

Conclusion

Monitoring the balance between circulating CD8+ TEMRA T cells and regulatory cell subsets and their transcripts may help to distinguish transplant recipients with operational tolerance from recipients at risk of graft loss.