title: Cytomegalovirus-responsive γδ T cells: novel effector cells in antibody-mediated kidney allograft microcirculation lesions.
abstract: 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.
authors.affiliation: University of Bordeaux, Mixte Research Unit 5164, Bordeaux, France; National Center for Scientific Research (CNRS), Bordeaux, France; and Department of Nephrology, Transplantation, and Dialysis.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelet
authors.affiliation: University of Bordeaux, Mixte Research Unit 5164, Bordeaux, France; National Center for Scientific Research (CNRS), Bordeaux, France; and Department of Nephrology, Transplantation, and Dialysis.
authors.forename: Lionel
authors.initials: L
authors.lastname: Couzi
authors.affiliation: University of Bordeaux, Mixte Research Unit 5164, Bordeaux, France; National Center for Scientific Research (CNRS), Bordeaux, France; and.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pitard
authors.affiliation: University of Bordeaux, Mixte Research Unit 5164, Bordeaux, France; National Center for Scientific Research (CNRS), Bordeaux, France; and.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sicard
authors.affiliation: Department of Nephrology, Transplantation, and Dialysis.
authors.forename: Claire
authors.initials: C
authors.lastname: Rigothier
authors.affiliation: Department of Pathology, and.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lepreux
authors.affiliation: University of Bordeaux, Mixte Research Unit 5164, Bordeaux, France; National Center for Scientific Research (CNRS), Bordeaux, France; and Laboratory of Immunology and Immunogenetics, University Hospital of Bordeaux, Bordeaux, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Moreau
authors.affiliation: University of Bordeaux, Mixte Research Unit 5164, Bordeaux, France; National Center for Scientific Research (CNRS), Bordeaux, France; and Laboratory of Immunology and Immunogenetics, University Hospital of Bordeaux, Bordeaux, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Taupin
authors.affiliation: University of Bordeaux, Mixte Research Unit 5164, Bordeaux, France; National Center for Scientific Research (CNRS), Bordeaux, France; and Department of Nephrology, Transplantation, and Dialysis.
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
authors.affiliation: University of Bordeaux, Mixte Research Unit 5164, Bordeaux, France; National Center for Scientific Research (CNRS), Bordeaux, France; and julie.dechanet@u-bordeaux2.fr.
authors.forename: Julie
authors.initials: J
authors.lastname: Déchanet-Merville
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002461:Cell Line, Transformed; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000473:pathology; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology; D058851:GPI-Linked Proteins / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D006650:Histocompatibility Testing; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation / Q000009:adverse effects*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008833:Microcirculation / Q000276:immunology; D008875:Middle Aged; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D007518:Isoantibodies; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017452:Receptors, IgG; D054353:Perforin
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