Cytomegalovirus-Responsive γδ T Cells

Abstract

Human cytomegalovirus infection in transplant recipients has been associated with adverse renal allograft outcome and with a large gd T-cell response, but whether both mechanisms are connected is unknown. We previously showed that most expanded circulating cytomegalovirus-responsive gd T cells express the Fcgreceptor CD16, suggesting that gd 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 gd T cells can perform antibody-dependent cellular cytotoxicity against stromal cells coated with donor-specific antibodies in vitro. In vivo, graft-infiltrating gd 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 gd 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 gd 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.

The Cell Biology of Cytomegalovirus: Implications for Transplantation

“…cd T cells have also been linked to allograft rejection by observations suggesting that cd T cells expressing the Fc-c receptor CD16 bind donor-specific antibodies and participate in allograft injury via ADCC (197). CMV-infected and immunized patients have increased numbers of cd T cells and higher levels of donor-specific antibodies (198). In vivo, graft-infiltrating cd T cells in close contact with ECs were more often observed in CMV-infected patients suffering antibody-mediated rejection than with T cell-mediated acute rejection (198).…”

“…CMV-infected and immunized patients have increased numbers of cd T cells and higher levels of donor-specific antibodies (198). In vivo, graft-infiltrating cd T cells in close contact with ECs were more often observed in CMV-infected patients suffering antibody-mediated rejection than with T cell-mediated acute rejection (198). The mechanisms underlying this effect are unclear but may involve the expression of "stress antigens" of CMV-infected cells recognized directly through the TCR (199).…”

Cytomegalovirus-Induced γδ T Cells During Rejection: An Ambivalent T Cell

“…We showed that CMV infection deeply reshapes the CD16þ lymphocyte compartment composition in CMVþ recipients who exhibit an equal amount of CD16þ natural killer (NK) cells and CD16þ Vd2 neg gd T cells (4). We also demonstrated that CMV-induced CD16þ Vd2 neg gd T cells could perform ADCC as well as NK cells by interacting with donor-specific antibodies and contribute to antibody-mediated microcirculation injuries during rejection (5). This implication of CMV-induced Vd2 neg gd T cells in antibody-mediated rejection seemingly contrasts with the regulatory function attributed to Vd1 gd T cells in this article (Figure 1).…”

Infectious Diseases in Transplantation—Report of the 20th Nantes Actualités Transplantation Meeting

“…Moreover, Dechanet-Merville reported that Vδ2 neg γδ T subsets may have a role during antibody-mediated rejection in patients harboring donorspecific antibodies. 8 In addition, γδ T subsets are able to recognize specific β2m-free empty HLA class I molecules 9 that are expressed at the cell surface on cellular responses to various stresses, including CMV infections or tumorigenesis. Another recently characterized unconventional T-cell subset with regulatory properties was presented by Guillaume Sarrabayrouse (Barcelona, Spain).…”