Cytomegalovirus-responsive ?? 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 ?? T-cell response, but whether both mechanisms are connected is unknown. We previously showed that most expanded circulating cytomegalovirus-responsive ?? T cells express the Fc?-receptor CD16, suggesting that ?? 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) ?? T cells can perform antibody-dependent cellular cytotoxicity against stromal cells coated with donor-specific antibodies in vitro. In vivo, graft-infiltrating ?? 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 ?? 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 ?? 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.

SUBMITTER: Bachelet T 

PROVIDER: S-EPMC4214528 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature