Date: Sunday, June 12, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
The transcription factor Eomesodermin (Eomes) is critical in the maintenance of antigen-specific memory T cells (Tmem). We have shown previously that prolonged kidney allograft survival in nonhuman primates (NHP) given regulatory dendritic cell infusion was associated with donor-specific Tmem exhibiting low Eomes and high cytotoxic T lymphocyte-associated protein 4 (CTLA4) expression. The role of Eomes in alloreactive Tmem is largely unknown. We characterized the phenotype and function of alloreactive Eomes+CD8+T cells in healthy humans and naïve rhesus monkeys.
Eomes expression by CD8+T cells was evaluated by flow cytometry. Eomes negative (neg), low (lo) and high (hi) subpopulations were assessed, before and after anti-CD3/CD28 bead activation or allo-stimulation. Intracellular cytokines (IFNg, TNFa, and IL-2), T-bet, Granzyme B and CTLA4 expression were examined.
Without activation, mean percentages of Eomesneg CD8+ T cells were 48.3 and 63.08%, Eomeslo 19.5 and 22.76%, Eomeshi 31.67 and 13.45%, in normal human and monkey PBMC respectively.
In humans, Eomeshi and Eomeslo populations comprised higher percentages of effector memory T cells while the Eomesneg subpopulation comprised higher percentages of naïve T cells than in monkeys.
In humans, Eomeshi and Eomeslo expressed higher levels of TNFa, INFg (T-bet) and Granzyme B, and lower levels of IL-2 compared to Eomesneg CD8+T cells. In monkeys the expression was similar among Eomeshi, Eomeslo and Eomesneg subpopulations, except for low Granzyme B expression by Eomeshi and low IL-2 expression by Eomeslo subpopulations.
Following CD3/CD28 activation or allo-stimulation, two distinct populations of Eomeslo and Eomeshi proliferating CD8+T cells were observed. In humans, CTLA4 expression was similar in Eomeslo and Eomeshi proliferating cells, while in monkeys, Eomeslo proliferating cells exhibited higher CTLA4 expression.
Following allo-stimulation, human and monkey Eomeshi proliferating cells expressed low levels of IL-2, but high levels TNFa, IFNg (T-bet), and Granzyme B compared to Eomeslo proliferating cells.
We show for the first time that despite similar memory phenotypes of Eomes+CD8+T cells in humans and NHP, their functions after allostimulation are dissimilar. Furthermore, variable expression of Eomes by CD8+T cells following allostimulation may correlate with diverse incidences of alloreactive Tmem in humans and NHP.
CITATION INFORMATION: Perez-Gutierrez A, Lu L, Zahorchak A, Ono Y, Thomson A, Ezzelarab M. Eomesodermin Expression by CD8+ Alloreactive T Cells in Human and Nonhuman Primate Allograft Recipients. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Perez-Gutierrez A, Lu L, Zahorchak A, Ono Y, Thomson A, Ezzelarab M. Eomesodermin Expression by CD8+ Alloreactive T Cells in Human and Nonhuman Primate Allograft Recipients. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/eomesodermin-expression-by-cd8-alloreactive-t-cells-in-human-and-nonhuman-primate-allograft-recipients/. Accessed January 20, 2021.
« Back to 2016 American Transplant Congress