Examination of a Novel Immunoregulatory Marker in Kidney and Lung Transplant Recipients
11Harvard Summer Research Program for Kidney Medicine, Harvard Medical School,, Boston, MA, 2Schuster Family Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Meeting: 2019 American Transplant Congress
Abstract number: D145
Keywords: FACS analysis, Kidney transplantation, Lung transplantation, T cells
Session Information
Session Name: Poster Session D: Lymphocyte Biology: Signaling, Co-Stimulation, Regulation
Session Type: Poster Session
Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory receptor mainly expressed on T cells and NK cells. TIGIT has been shown to be an immune checkpoint, and like PD-1, blockade of TIGIT has been shown increased cell proliferation, cytokine production, and degranulation of TA-specific CD8+ T cells and TIL CD8+ T cells in melanoma patients. Although TIGIT has been shown to play an important role in various autoimmune diseases and cancer, its role in transplantation remains unclear. We examined the expression levels of TIGIT and its receptor CD226 in kidney and lung transplant patients and healthy controls.
*Methods: Blood samples were collected from healthy individuals, kidney and lung transplant recipients and Peripheral blood mononuclear cells were isolated. Cell surface expression of CD226, TIGIT, CD155 and CD112 on peripheral T and NK cells were measured in a BD Canto II flow cytometer and data were analyzed using Flowjo.
*Results: We observed that in the two transplant recipient groups both T and NK cell populations showed a significant decrease in TIGIT and an increase in CD226 expression compared to healthy controls. The ratio of TIGIT:CD226 was significantly decreased in both the CD4+ and CD8+ T cells in both transplant groups versus healthy Controls (p=0.002, p=0.0017). Interestingly, in both the transplant recipient groups a similar and significant decrease in the TIGIT:CD226 ratio was also observed in the CD56+ NK cells (p<0.0001). CD226+ NK cells showed more heterogeneity in the KTR populations, whereas TIGIT+ NK cells showed heterogeneity in the control population. We did not observe any significant expression of CD155 or CD112 in any of the above cell populations or groups. Correlation of TIGIT and CD226 expression with clinical characteristics of the kidney transplant recipients is currently in progress.
*Conclusions: Increased expression of CD226 in both T and NK cell populations is observed in lung and kidney transplant recipients. CD226 is enhanced in both transplant populations versus HC, and is likely to be related to long term antigenic exposure to alloantigens. It may be possible to determine an optimal TIGIT:CD226 ratio that may predict allograft acceptance.
To cite this abstract in AMA style:
Desai AD, Kavalam GJ, Chandraker A, Tripathi S. Examination of a Novel Immunoregulatory Marker in Kidney and Lung Transplant Recipients [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/examination-of-a-novel-immunoregulatory-marker-in-kidney-and-lung-transplant-recipients/. Accessed December 10, 2024.« Back to 2019 American Transplant Congress