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Kidney Week

Abstract: FR-PO1120

Examination of a Novel Emerging Immune Checkpoint in Kidney Transplant Recipients

Session Information

  • Transplantation: Basic
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 1901 Transplantation: Basic

Authors

  • Kavalam, George J., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Desai, Amar D., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Chandraker, Anil K., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Tripathi, Sudipta, Brigham and Women's Hospital, Boston, Massachusetts, United States
Background

The balance between T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) and its co-receptor CD226 function as an ‘immune checkpoint’ with immunomodulatory functions in both T and NK cells. Immunomodulation is mediated through the balance of TIGIT/CD226 binding with the ligands CD155/CD112. Interaction of CD226 with the ligands CD155 and CD112 co-stimulates T cell, whereas TIGIT exerts the opposite effect and inhibits T cell response.
This ligand/receptor network plays an important role in various autoimmune diseases and cancer, but its role in transplantation remains unclear. We examined the expression levels of TIGIT, CD226 and their ligands CD155 and CD112 in kidney transplant recipients (KTR) and healthy controls (HC) to understand the relevance of TIGIT/CD226 co-signaling in transplantation.

Methods

Blood samples were collected from 23 HC and 68 KTR and cell surface expression of CD226, TIGIT, CD155 and CD112 and other cell markers on peripheral T and NK cells were determined by flow cytometry.

Results


We observed that in the KTR group both T and NK cell populations showed a significant decrease in TIGIT and an increase in CD226 expression compared to HC. Interestingly, in the KTR CD4+ T cells showed a significant increase in CD226 expression whereas CD8+ T cells showed a significant decrease in TIGIT expression. Both these changes lead to an increase in IFN-γ production and a pro-inflammatory environment.
The predominant peripheral CD16+ NK cells also showed an inflammatory phenotype with both increased CD226 expression and decreased TIGIT expression and also showed a significant increase in the expression of both the ligands CD155 and CD112 in comparison to HC.

Conclusion


Increased expression of CD226 in both T and NK cells and increased expression of its ligands CD155 and CD112 on NK cell populations were observed in KTR, suggesting a pro-inflammatory phenotype and a pluasible NK-T cell-cell interaction in the periphery. The TIGIT/CD226 axis members are potential targets for reducing the alloimmune response mediated by T and NK cells.