Date: Tuesday, June 5, 2018
Session Time: 2:30pm-4:00pm
Presentation Time: 2:54pm-3:06pm
Location: Room 602/603/604
Memory T cell responses play a critical role in the outcome of allo-transplantation. While the role of the T-box transcription factor Eomesodermin (Eomes) in the maintenance of antigen-specific Tmem is well studied, little is known about Eomes+CD8+T cell responses after transplantation. We evaluated allo-reactive Eomes+CD8+T cells in healthy volunteers and kidney transplant patients and their relation to transplant (tx) outcome.
Three groups of patients were analyzed: patients with no rejection within the first year post-tx (n=11), patients with subclinical rejection (n=5), and patients with acute cellular rejection (n=5). All patients received Thymoglobulin induction and immunosuppression based on Tacrolimus, Mofetilmicophenolate and Prednisone. Cryopreserved peripheral blood mononuclear cell (PBMC) from kidney recipients were stained with CFSE and co-cultured with irradiated donor PBMC. Proliferation was determined by CFSE dilution. Eomes, Tbet and cytokines (IFNg, TNFa) were assessed by flow cytometry.
High Eomes expression by steady-state CD8+T cells correlated with effector and memory phenotype. Following allo-stimulation, expression of both the T-box proteins Eomes and T-bet by proliferating cells increased significantly, where Eomes and T-bet co-expression correlated with a high incidence of IFNγ+TNFα+ CD8+T cells. In patients exhibiting no rejection, Eomes but not T-bet expression by donor-stimulated CD8+T cells increased significantly after transplantation. This was associated with a significant increase in the EomeshiT-betlo and a significant decrease in the EomesloT-bethi CD8+T cell subsets. Interestingly, before transplantation, there were significantly higher incidences of donor-stimulated EomeshiT-betlo CD8+T cells in patients without subsequent rejection, and significantly higher incidences of donor-stimulated EomeshiT-bethi CD8+T cells in those that subsequently exhibited cellular rejection.
These findings indicate that Eomes but not T-bet is upregulated by donor-reactive CD8+T cells early after transplant in patients without rejection. Also, concomitant high Eomes and T-bet expression by donor allo-stimulated CD8+T cells is associated with enhanced effector function and may correlate with an increased incidence of rejection.
CITATION INFORMATION: Perez-Gutierrez A., Metes D., Hariharan S., Thomson A., Ezzelarab M. Donor Reactive Eomesderminhi CD8+ T Cells Are Significantly Upregulated Early after Transplant in Kidney Transplant Patients without Rejection Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Perez-Gutierrez A, Metes D, Hariharan S, Thomson A, Ezzelarab M. Donor Reactive Eomesderminhi CD8+ T Cells Are Significantly Upregulated Early after Transplant in Kidney Transplant Patients without Rejection [abstract]. https://atcmeetingabstracts.com/abstract/donor-reactive-eomesderminhi-cd8-t-cells-are-significantly-upregulated-early-after-transplant-in-kidney-transplant-patients-without-rejection/. Accessed October 22, 2020.
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