Back Signaling of HLA Class I Molecules and NK Cell Receptor Ligands in Renal Epithelial Cells Contributes to the Rejection-Specific Microenvironment

E. Chichelnitskiy¹, J. Egelkamp¹, K. Daemen¹, J. Keil¹, C. Neudörfl¹, J. Bräsen², J. Schmitz², H. Haller³, C. Blume⁴, C. Falk⁵

¹Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany, ²Nephropathology Unit, Institute of Pathology, Hannover Medical School, Hannover, Germany, ³Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany, ⁴Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
Institute of Technical Chemistry, Leibniz University, Hannover, Germany, ⁵Institute of Transplant Immunology, Hannover Medical School
DZIF, German Center for Infection Research, TTU-IICH, Hannover/Braunschweig, Germany

Meeting: 2019 American Transplant Congress

Abstract number: A196

Keywords: HLA antibodies, Kidney, Natural killer cells, Rejection

Session Information

Session Name: Poster Session A: Kidney Chronic Antibody Mediated Rejection

Session Type: Poster Session

Date: Saturday, June 1, 2019

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

Presentation Time: 5:30pm-7:30pm

Location: Hall C & D

*Purpose: During the last years, diverse harming mechanisms of donor-specific antibodies (DSA) to endothelial cells have been studied accompanied by an emerging evidence of NK cell involvement in antibody-mediated rejection (ABMR). However, the role of kidney epithelial cells was less intensively examined and maybe underestimated despite their potential impact as targets for DSA and NK cells.

*Methods: Therefore, we investigated proximal tubular epithelial cells (PTEC) upon stimulation via HLA class I and NK cell receptor ligands, CD155 and CD166, which were selected based on their potential signal-transducing capacities.

*Results: Upon stimulation with anti-HLA and anti-CD166 mab, PTEC secreted IL-6, CXCL8, CXCL10, IL-12p40, IL-1RA, and sICAM-1 (all p<0.05). Clinically approved immunosuppressive drugs and other signal inhibitors were unable to block this back signaling and, hence, revealed a complex regulatory network upon triggering HLA class I and NK cell receptor ligands. This PTEC cytokine response was compared to the cytokine/chemokine microenvironment of 37 kidney transplant biopsies, classified as unsuspicious, T-cell-mediated rejection (TCMR), borderline or ABMR rejection according to the BANFF classification. Rejection, especially ABMR, was associated with a distinct cytokine milieu, guided by significantly higher levels of chemokines (CXCL9, CXCl10 and CCL5, all p<0.05).

*Conclusions: Based upon, we suggest, that via PTEC back signaling, chemokine release strengthens the ABMR-process by attraction of other immunocytes and this contributes to the destructing pathomechanisms within kidney allograft rejection.

To cite this abstract in AMA style:

Chichelnitskiy E, Egelkamp J, Daemen K, Keil J, Neudörfl C, Bräsen J, Schmitz J, Haller H, Blume C, Falk C. Back Signaling of HLA Class I Molecules and NK Cell Receptor Ligands in Renal Epithelial Cells Contributes to the Rejection-Specific Microenvironment [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/back-signaling-of-hla-class-i-molecules-and-nk-cell-receptor-ligands-in-renal-epithelial-cells-contributes-to-the-rejection-specific-microenvironment/. Accessed May 11, 2025.

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