Characterization of eomesodermin and T‐bet expression by allostimulated CD8 + T cells of healthy volunteers and kidney transplant patients in relation to graft outcome

Memory T cell (Tmem) 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 the phenotype and function of allo‐reactive Eomes + CD8 + T cells in healthy volunteers and kidney transplant patients and their relation to transplant outcome. High Eomes expression by steady‐state CD8 + T cells correlated with effector and memory phenotype. Following allo‐stimulation, the expression of both the T‐box proteins Eomes and T‐bet by proliferating cells increased significantly, where high expression of Eomes and T‐bet correlated with higher incidence of allo‐stimulated IFNγ + TNFα + CD8 + T cells. In patients with no subsequent rejection, Eomes but not T‐bet expression by donor‐stimulated CD8 + T cells, increased significantly after transplantation. This was characterized by increased Eomes hi T‐bet ‐/lo and decreased Eomes ‐/lo T‐bet hi CD8 + T cell subsets, with no significant changes in the Eomes hi T‐bet hi CD8 + T cell subset. No upregulation of exhaustion markers programmed‐death‐1 (PD‐1) and cytotoxic‐T‐lymphocyte‐associated‐antigen‐4 (CTLA4) by donor‐stimulated Eomes + CD8 + T cells was observed. Before transplantation, in patients without rejection, there were higher incidences of Eomes hi T‐bet ‐/lo , and lower incidences of Eomes hi T‐bet hi and Eomes ‐/lo T‐bet hi donor‐stimulated CD8 + T cell subsets, compared to those with subsequent rejection. Overall, our findings indicate that high Eomes expression by allo‐stimulated T‐bet + CD8 + T cells is associated with enhanced effector function, and that an elevated incidence of donor‐stimulated CD8 + T cells co‐expressing high levels of Eomes and T‐bet before transplantation, may correlate with an increased incidence of acute cellular rejection.