Cytomegalovirus-responsive γδ T cells: novel effector cells in antibody-mediated kidney allograft microcirculation lesions

J Am Soc Nephrol. 2014 Nov;25(11):2471-82. doi: 10.1681/ASN.2013101052. Epub 2014 Apr 17.


Human cytomegalovirus infection in transplant recipients has been associated with adverse renal allograft outcome and with a large γδ T-cell response, but whether both mechanisms are connected is unknown. We previously showed that most expanded circulating cytomegalovirus-responsive γδ T cells express the Fcγ-receptor CD16, suggesting that γδ T cells may participate in allograft lesions mediated by donor-specific antibodies through antibody-dependent cellular cytotoxicity. Here, we show that cytomegalovirus-specific CD16(pos) γδ T cells can perform antibody-dependent cellular cytotoxicity against stromal cells coated with donor-specific antibodies in vitro. In vivo, graft-infiltrating γδ T cells localized in close contact with endothelial cells only in patients who experienced cytomegalovirus infection and were more frequent within peritubular capillaries and glomeruli from antibody-mediated acute rejections than within those from T cell-mediated acute rejections. Finally, a persistently increased percentage of circulating cytomegalovirus-induced γδ T cells correlated inversely with the 1-year eGFR only in kidney recipients with donor-specific antibodies. Collectively, these data support the conclusion that cytomegalovirus-induced γδ T cells are involved in, and may serve as a clinical biomarker of, antibody-mediated lesions of kidney transplants. Moreover, these findings offer a new physiopathologic link between cytomegalovirus infection and allograft dysfunction in recipients with donor-specific antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Line, Transformed
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / pathology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / immunology
  • GPI-Linked Proteins / immunology
  • Graft Rejection / immunology*
  • Histocompatibility Testing
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Isoantibodies / immunology*
  • Kidney Transplantation / adverse effects*
  • Killer Cells, Natural / immunology
  • Male
  • Microcirculation / immunology
  • Middle Aged
  • Perforin
  • Pore Forming Cytotoxic Proteins / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Receptors, IgG / immunology
  • Transplantation, Homologous
  • Young Adult


  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Isoantibodies
  • PRF1 protein, human
  • Pore Forming Cytotoxic Proteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, IgG
  • Perforin