Granzyme B producing B-cells in renal transplant patients

Clin Immunol. 2017 Nov:184:48-53. doi: 10.1016/j.clim.2017.04.016. Epub 2017 Apr 28.

Abstract

Objectives: A separate subset of Granzyme B (GrB) producing B-cells regulating T-cell mediated immunity has been identified. In the present study, we investigated the role of GrB+ B-cells in renal transplant patients (RTX).

Methods: 12 healthy controls (HC) and 26 RTX patients were enrolled. In addition, 19 healthy volunteers treated with cyclosporine A (CsA) were enrolled. GrB+ B-cells were determined via flow cytometry.

Results: RTX Patients showed a diminished fraction of GrB+ B-cells as compared to HC. CsA treatment of healthy volunteers had no impact on the development of GrB+ B-cells. RTX patients with a history of allograft rejection showed an increased frequency of GrB+ B-cells. RTX patients with at least one episode of CMV viremia tended to have lower GrB+ B-cells as compared to patients without viremic episodes.

Conclusion: We demonstrate that treatment with CsA does not impair the development of GrB+ B-cells. GrB+ B-cells may have a dual role in renal transplantation as regulatory cells to maintain allospecific tolerance and as effector cells enhancing viral control.

Keywords: Allograft rejection; B-cells; Immune tolerance; Regulatory B-cells; Renal transplantation.

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Aged
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / metabolism*
  • Case-Control Studies
  • Cyclosporine / pharmacology
  • Cyclosporine / therapeutic use
  • Female
  • Graft Rejection / prevention & control
  • Granzymes / drug effects
  • Granzymes / metabolism*
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Interleukins / pharmacology
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Mycophenolic Acid / therapeutic use
  • Tacrolimus / therapeutic use

Substances

  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Interleukins
  • Cyclosporine
  • GZMB protein, human
  • Granzymes
  • Mycophenolic Acid
  • interleukin-21
  • Tacrolimus