NK Cells Play a Critical Role in Mediating Inflammation and Graft Failure During Antibody-Mediated Rejection of Kidney Allografts.

T. Tanaka,^1,2 N. Kohei,¹ N. Dvorina,¹ A. Valujskikh,¹ W. Baldwin 3rd,¹ R. Fairchild.¹

¹Department of Immunology, Cleveland Clinic, Cleveland, OH
²Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Meeting: 2016 American Transplant Congress

Abstract number: 473

Keywords: Alloantibodies, Kidney transplantation, Mice, Natural killer cells

Session Information

Session Name: Concurrent Session: B cells and Antibody-Mediated Rejection: Animal Models

Session Type: Concurrent Session

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 November 25, 2024.

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