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T Cell Exhaustion in Kidney Transplant Patients

M. Fribourg,1 C. Fischman,2 L. Anderson,2 B. Burrell,3 P. Heeger,2 P. Cravedi.2

1Department of Neurology, Icahn School of Medicine, New York
2Department of Medicine, Icahn School of Medicine, New York
3Immune Tolerance Network, Bethesda.

Meeting: 2018 American Transplant Congress

Abstract number: 403

Keywords: Induction therapy, Kidney transplantation, T cells

Session Information

Date: Tuesday, June 5, 2018

Session Name: Concurrent Session: Biomarkers, Immune Monitoring and Outcomes: Basic

Session Time: 2:30pm-4:00pm

 Presentation Time: 2:30pm-2:42pm

Location: Room 602/603/604

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Background: T cell exhaustion is a dysfunctional state that arises during chronic infection and cancer in response to persistence of high antigenic load. Whether chronic exposure to graft alloantigens leads to the formation of exhausted T cells (Tex) and, if so, whether Tex is related to graft outcome in human kidney transplant recipients is unknown.

Methods: We used mass cytometry (CyTOF) to analyze exhaustion phenotypes of serially collected PBMC from 26 kidney transplant recipients enrolled in the prospective, observational, CTOT-01 cohort (samples were obtained at month 0, 3, and 6 after transplant). Using a panel of 36 markers and unbiased clustering algorithms (Phenograph) we extracted the frequencies of 5 CD4+ and 2 CD8+ T cell subsets expressing different combination of exhaustion markers (Figure 1A).

Results: We observed significant increases in the percentages of circulating CD4+ Tex and CD8+ Tex from month 0 to month 6 in patients given induction therapy with anti-thymocyte globulin (ATG) compared to those given basiliximab or no induction (Figure 1B-C). Within the Tex cells, the subsets of CD4+TIGIT+TIM3-2b4- and CD8+TIGIT+2b4+41BB-TIM3- were the most differentially increased between the two induction strategies. Percentages of CD8+TIGIT+2b4+41BB-TIM3- at 6 months correlated inversely with increasing interstitial fibrosis between 0 and 6 month surveillance graft biopsies (r:-0.54; p=0.05).

Discussion: Our findings identify previously unrecognized relationships among peripheral blood T cell exhaustion phenotypes, progressive kidney allograft injury and ATG induction and raise the possibility that these observations are mechanistically linked.

CITATION INFORMATION: Fribourg M., Fischman C., Anderson L., Burrell B., Heeger P., Cravedi P. T Cell Exhaustion in Kidney Transplant Patients Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Fribourg M, Fischman C, Anderson L, Burrell B, Heeger P, Cravedi P. T Cell Exhaustion in Kidney Transplant Patients [abstract]. https://atcmeetingabstracts.com/abstract/t-cell-exhaustion-in-kidney-transplant-patients/. Accessed March 8, 2021.

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