Introduction

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.

Methods

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.

Results

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 Eomes^hiT-bet^lo and a significant decrease in the Eomes^loT-bet^hi CD8+T cell subsets. Interestingly, before transplantation, there were significantly higher incidences of donor-stimulated Eomes^hiT-bet^lo CD8+T cells in patients without subsequent rejection, and significantly higher incidences of donor-stimulated Eomes^hiT-bet^hi CD8+T cells in those that subsequently exhibited cellular rejection.

Conclusions

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 Eomesdermin^hi CD8⁺ T Cells Are Significantly Upregulated Early after Transplant in Kidney Transplant Patients without Rejection Am J Transplant. 2017;17 (suppl 3).

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