CD56dimCD16bright NK Cells from Kidney Transplant Recipients with Antibody-mediated Rejection Display Increased Proliferation, Type-1 Activation and Cytotoxic Profile

CD56^dimCD16^bright NK Cells from Kidney Transplant Recipients with Antibody-mediated Rejection Display Increased Proliferation, Type-1 Activation and Cytotoxic Profile

E. Bailly¹, C. Macedo¹, K. Louis¹, B. Ramaswami¹, M. Lucas¹, C. Bentlejewski¹, P. Randhawa¹, A. Zeevi¹, C. Lefaucheur², D. Metes¹

¹Department of Surgery, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, ²INSERM UMR-S976. Endothelium, Inflammation & Alloreactivity, Université de Paris, Paris, France

Meeting: 2021 American Transplant Congress

Abstract number: 324

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

Topic: Clinical Science » Kidney » Kidney Acute Antibody Mediated Rejection

Session Information

Session Name: Kidney Antibody Mediated Rejection

Session Type: Rapid Fire Oral Abstract

Date: Tuesday, June 8, 2021

Session Time: 4:30pm-5:30pm

Presentation Time: 5:05pm-5:10pm

Location: Virtual

*Purpose: CD56^dimCD16^bright NK cells are highly potent for cytotoxicity through cell-mediated cytotoxicity (CMC), antibody-dependent cell-mediated cytotoxicity (ADCC) and INF-γ production. The contribution of NK cells to antibody-mediated rejection (ABMR) injuries have been highlighted through transcriptomic analysis and immunohistochemistry of kidney and heart allograft biopsies. However, description of circulating NK cells profiles during ABMR is lacking.

*Methods: Deep phenotypic analysis of circulating CD56^dimCD16^bright NK cells using 25-color spectral flow cytometry was implemented in 68 kidney transplant (KTx) recipients: (i) 17 donor specific anti-HLA antibody (DSA) free of ABMR, (ii) 17 DSA+ biopsy-proven mixed ABMR (DSA+ABMR+), (iii) 17 stable free of DSA/rejection, (iv) 17 T-cell mediated rejection and 17 healthy controls. Samples were analyzed at the time of rejection, of first DSA occurrence or at a matching time point in stable patients. Functional assays were performed in 8 patients from each group, consisting of 6-hours coculture of PBMC with T2 lymphoblastic cells (TAP-deficient, HLA-A2 expressor) + anti-HLA-A2+ serum.

*Results: CD56^dimCD16^bright NK cells from DSA+ABMR+ patients, when compared to the other groups, significantly proliferated (Ki67+) and selectively up-regulated IL-2R/-15Rβ chain and IL-21R, suggesting their higher responsiveness to common γc cytokines that support NK cell survival/proliferation and cytotoxicity. Moreover, they co-expressed significant elevated levels of EOMES and T-bet, as well as of CD16A/FcγRIIIA-inducible CD160 and CD161/NK1.1, cytotoxicity markers that reflect their higher Type-1 activation status. Indeed, CD56^dimCD16^bright NK cells from DSA+ABMR+ patients displayed increased INF-γ and TNF-α/IL-10 ratios in ADCC and CMC assays. CXCR3 overexpression was noted suggesting a higher migration potential towards inflamed tissues.

*Conclusions: Significant NK cell phenotypic and functional changes occur during ABMR with potential involvement to allograft injury. Early detection of proliferating, activated, cytotoxic CD56^dimCD16^brightNK cells in the blood of patients with ABMR could help for timely therapeutic intervention.

To cite this abstract in AMA style:

Bailly E, Macedo C, Louis K, Ramaswami B, Lucas M, Bentlejewski C, Randhawa P, Zeevi A, Lefaucheur C, Metes D. CD56^dimCD16^bright NK Cells from Kidney Transplant Recipients with Antibody-mediated Rejection Display Increased Proliferation, Type-1 Activation and Cytotoxic Profile [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/cd56dimcd16bright-nk-cells-from-kidney-transplant-recipients-with-antibody-mediated-rejection-display-increased-proliferation-type-1-activation-and-cytotoxic-profile/. Accessed November 21, 2024.

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