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

• Published in: Journal of the American Society of Nephrology 2014-11, Vol.25 (11), p.2471-2482
• Main Authors: Bachelet, Thomas, Couzi, Lionel, Pitard, Vincent, Sicard, Xavier, Rigothier, Claire, Lepreux, Sébastien, Moreau, Jean-François, Taupin, Jean-Luc, Merville, Pierre, Déchanet-Merville, Julie
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Basic Research; 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
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2013101052

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.