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

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

Author information

1
University of Bordeaux, Mixte Research Unit 5164, Bordeaux, France; National Center for Scientific Research (CNRS), Bordeaux, France; and Department of Nephrology, Transplantation, and Dialysis.
2
University of Bordeaux, Mixte Research Unit 5164, Bordeaux, France; National Center for Scientific Research (CNRS), Bordeaux, France; and.
3
Department of Nephrology, Transplantation, and Dialysis.
4
Department of Pathology, and.
5
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.
6
University of Bordeaux, Mixte Research Unit 5164, Bordeaux, France; National Center for Scientific Research (CNRS), Bordeaux, France; and julie.dechanet@u-bordeaux2.fr.

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.

PMID:
24744438
PMCID:
PMC4214528
DOI:
10.1681/ASN.2013101052
[Indexed for MEDLINE]
Free PMC Article

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