Session Time: 4:30pm-5:30pm
Presentation Time: 5:05pm-5:10pm
*Purpose: CD56dimCD16bright 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 CD56dim CD16bright 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: CD56dimCD16bright 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, CD56dimCD16bright 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 CD56dimCD16bright NK 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. CD56dimCD16bright 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 June 12, 2021.
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