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Recipient Treatment with Anti-CD122 mAb Prolongs Kidney Allograft Survival During Antibody-Mediated Rejection without Impacting NK Cell Activation within the Graft

D. Okada, S. Miyairi, N. Dvorina, K. S. Keslar, A. Valujskikh, W. Baldwin, R. Fairchild

Cleveland Clinic, Cleveland, OH

Meeting: 2022 American Transplant Congress

Abstract number: 631

Keywords: Antibodies, Mice, knockout, Natural killer cells, Rejection

Topic: Basic Science » Basic Science » 02 - Acute Rejection

Session Information

Session Name: Acute Rejection

Session Type: Poster Abstract

Date: Saturday, June 4, 2022

Session Time: 5:30pm-7:00pm

 Presentation Time: 5:30pm-7:00pm

Location: Hynes Halls C & D

*Purpose: Dysregulated donor-specific antibody (DSA) responses are induced in B6.CCR5-/- mice transplanted with complete MHC mismatched kidney allografts and are required for rejection of the grafts between days 18 and 30 post-transplant. Acute antibody-mediated rejection (AMR) also requires NK cell activation to proliferate and express effector functions within the graft. Depletion or inactivation of graft infiltration NK cells results in long-term survival of kidney allografts despite high DSA titers.

*Methods: Since NK cell homeostasis and proliferation are dependent on IL-15, we then tested the impact of anti-CD122 mAb to inhibit IL-15 signaling on kidney allograft survival and NK cell activation within A/J kidneys transplanted to B6.CCR5-/- recipients.

*Results: On day 15, graft-infiltrating NK cell activation to proliferate and express CD107a was equivalent within allografts in control and anti-CD122 mAb treated B6.CCR5-/- recipients and was accompanied with similar graft expression of transcripts associated with NK cell, including SH2D1B1 and IFN-g. In contrast to lack of efficacy for NK cells, anti-CD122 mAb was a very effective inhibitor of memory T cell activation within allografts. Despite the inability to inhibit NK cell activation in kidney allografts, anti-CD122 mAb treatment of B6.CCR5-/- recipients extended survival of 50% (n = 5) of the allografts to between days 55 and 120, with an overall median survival time of 58 days. However, kidney allografts from anti-CD122 mAb- and control- treated recipients exhibited intense C4d deposits in peritubular capillaries indicating no histopathologic difference in graft injury.

*Conclusions: Overall, the results suggest that strategies inhibiting recruitment and activation of T cells in kidney allografts may not be effective in inhibiting activation of kidney allograft-infiltrating NK cells during ABMR.

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To cite this abstract in AMA style:

Okada D, Miyairi S, Dvorina N, Keslar KS, Valujskikh A, Baldwin W, Fairchild R. Recipient Treatment with Anti-CD122 mAb Prolongs Kidney Allograft Survival During Antibody-Mediated Rejection without Impacting NK Cell Activation within the Graft [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/recipient-treatment-with-anti-cd122-mab-prolongs-kidney-allograft-survival-during-antibody-mediated-rejection-without-impacting-nk-cell-activation-within-the-graft/. Accessed May 30, 2025.

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