Session Time: 3:15pm-4:45pm
Presentation Time: 4:03pm-4:15pm
*Purpose: Contribution of NK cells to antibody-mediated rejection (ABMR) injuries have recently been highlighted through transcriptomic analysis and immunohistochemistry of kidney and heart allograft biopsies. However, till date there are no available data to corroborate these findings with blood circulating NK cells profiles in ABMR.
*Methods: Here we aimed for a comprehensive examination of the phenotype of circulating CD56brightCD16dim and CD56dimCD16bright NK cells gated out of CD3-CD19-CD14-CD7+ using 25 color spectral flow cytometry in 9 kidney transplant (KTx) recipients: (i) donor specific anti-HLA antibody free of ABMR (DSA+ABMR-), (ii) DSA+ biopsy-proven ABMR (DSA+ABMR+), (iii) stable patients (DSA-) and (iv) 6 healthy controls (HC), the cohort currently being enlarged. Cross-sectional samples were analyzed at the time of first DSA detection or of ABMR occurring in the 3 first months post-KTx.
*Results: Overall, NK cells from KTx patients undergoing DSA+ABMR+ significantly proliferated according to Ki67 staining (62±30.3% in DSA+ABMR+, 30.6±14.1% in DSA+ABMR-, 18.2±2.7% in DSA-, 4.5±1.3% in HC, p=0.024). Interestingly, the upstream transcriptional regulator TCF7 uniquely expressed by CD56brightCD16dim from HC was decreased in all patients except for DSA+ABMR+ patients, who maintained its levels’ elevated. Moreover, de novo TCF7 expression was detected in the CD56dimCD16bright subset from DSA+ABMR+ patients (26.9±14.7% in DSA+ABMR+ vs 2.5±1.9% DSA+ABMR- vs 3.6±1.2% DSA- vs 8.2±9.4% in HC, p=0.05), subset that also selectively up-regulated IL-21R and IL-2/-15Rβ, thus supporting its possible self-renewal capacity, responsiveness to common γc cytokines and long-term persistence. In DSA+ABMR+ patients, unlike for the other groups, the CD56dimCD16bright NK subset co-expressed significant elevated levels of the Th1-promoting transcription factors EOMES (p=0.023) and T-bet, of the chemokine receptor CXCR3 (p=0.001), as well as of the activation NKG2D (p=0.007) and of the CD16a-inducible and cytotoxicity CD160 (p=0.017) markers, suggesting their activation status, potential for migration towards inflamed tissues and enhanced cytotoxicity via CD16.
*Conclusions: In conclusion, here we have identified significant NK cell phenotypic changes within CD56dimCD16bright subset during ABMR, with potential functional consequences to allograft injury. Early detection of proliferating, activated, cytotoxic, and with self-renewal features CD56dimCD16bright NK cells in the blood of patients with ABMR would help for timely therapeutic intervention.
To cite this abstract in AMA style:Bailly EA, Louis K, Macedo C, Ramaswami B, Lucas M, Zeevi A, Lefaucheur C, Metes D. CD56DimCD16Bright NK Cells from Kidney Transplant Recipients with Antibody-Mediated Rejection Display Increased Proliferation, Self-Renewal, Pro-Inflammatory and Cytotoxic Profile [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/cd56dimcd16bright-nk-cells-from-kidney-transplant-recipients-with-antibody-mediated-rejection-display-increased-proliferation-self-renewal-pro-inflammatory-and-cytotoxic-profile/. Accessed March 3, 2021.
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