Date: Tuesday, June 14, 2016
Session Time: 4:30pm-6:00pm
Presentation Time: 5:30pm-5:42pm
Location: Room 309
While the incidence of antibody-mediated kidney graft rejection has increased, the key cellular and molecular participants underlying this graft injury remain unclear. We have previously reported that rejection of kidney allografts in CCR5-/- mice is dependent on production of donor-specific antibody. The goal of the current study was to determine if cells expressing cytotoxic function contributed to antibody-mediated kidney allograft rejection in these recipients. Wild type C57BL/6, B6.CCR5-/- and CD8-/-/CCR5-/- mice were transplanted with complete MHC mismatched A/J kidney grafts and intra-graft inflammatory components were followed to rejection. B6.CCR5-/- and CD8-/-/CCR5-/- recipients rejected kidney allografts by day 35 whereas 65% of allografts in wild type recipients survived past day 80 post-transplant. Allograft rejection in wild type recipients was associated with high titers of donor-specific antibody, equivalent to those induced in the CCR5-deficient recipients. Rejected allografts in C57BL/6, B6.CCR5-/- and CD8-/-/CCR5-/- recipients expressed high levels of VCAM-1 and MMP7 mRNA that was associated with high serum titers of donor-specific antibody. At rejection in wild type and CD8-/-/CCR5-/- recipients, kidney allografts also expressed genes associated with NK cell (Sh2d1B1 and MYBL1) but not with T cell (CXCR6) activity during inflammation. High levels of perforin and granzyme B mRNA expression in kidney allografts peaked on day 6 post-transplant in all recipients, but were absent in isografts. Depletion of NK cells in CD8-/-/CCR5-/- recipients reduced this expression to background levels and promoted the long-term survival of 40% of the kidney allografts. These results support a role for NK cells in increasing inflammation during antibody-mediated kidney allograft injury and in rejection of the grafts.
CITATION INFORMATION: Tanaka T, Kohei N, Dvorina N, Valujskikh A, Baldwin 3rd W, Fairchild R. NK Cells Play a Critical Role in Mediating Inflammation and Graft Failure During Antibody-Mediated Rejection of Kidney Allografts. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Tanaka T, Kohei N, Dvorina N, Valujskikh A, 3rd WBaldwin, Fairchild R. NK Cells Play a Critical Role in Mediating Inflammation and Graft Failure During Antibody-Mediated Rejection of Kidney Allografts. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/nk-cells-play-a-critical-role-in-mediating-inflammation-and-graft-failure-during-antibody-mediated-rejection-of-kidney-allografts/. Accessed July 4, 2020.
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