Date: Tuesday, June 4, 2019
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: The T-box transcription factors Eomesodermin (Eomes) and T-bet play a critical role in differentiation and function of CD8+ memory T cells (Tmem). We have previously shown, that in humans, high Eomes expression by allo-reactive CD8+T cells correlates with enhanced effector function. Our purpose was to evaluate the phenotypic and functional differences of alloreactive Eomeshi CD8+ T cells in human and nonhuman primates.
*Methods: Healthy human and juvenile rhesus monkey T cells were purified followed by co-culture with allogeneic T-cell depleted peripheral blood mononuclear cells (PBMC). CD8+Tmem subsets were identified based on CD45RA/CD28 expression. Eomes expression by nonactivated and allo-activated CD8+ T cells was evaluated. The expression of T-bet, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), Programmed cell death-1 (PD-1) and effector cytokines (TNFα and IFNγ) were assessed.
*Results: Before allo-stimulation, human and monkey Eomeshi CD8+T cells comprised high percentage of CD45RA-CD28+ central memory T cells, while Eomeslo CD8+T cells comprised higher percentage of CD45RA+CD28+ naïve T cells. Additionally, human but not monkey Eomeshi CD8+T cells exhibited higher percentages of TNFα/IFNγ double positive cells, than Eomeslo CD8+T cells.T-bet expression was higher in human, but lower in monkey Eomeshi, compared to Eomeslo CD8+T cells. After allo-stimulation, the percentages of Tmem subsets was variable in both humans and monkeys CD8+ T cells. While both human and monkey Eomeshi CD8+T-cells exhibited significantly higher TNFα/IFNγ double positive cells, than Eomeshi CD8 T cells, only human but not monkey Eomeshi CD8+T cells express significantly higher T-bet than Eomeslo CD8+ T cells. In proliferating cells, high percentages of TNFα/INFγ double positive cells were observed in human Eomeshi Tbethi and monkey EomeshiTbetlo CD8+T cell subsets.
CTLA4 expression was significantly upregulated by CD8+T cells after allo-stimulation in both human and monkeys, where in monkeys, but not humans, an inverse correlation between Eomes and CTLA4 expression was observed by allo-stimulated CD8+ T cells. While co-expression of PD-1 and CTLA4 was comparable between Eomeshi and Eomeslo CD8+T cells in humans, the co-expression of PD-1 and CTLA4 was significantly lower in Eomeshi compared to Eomeslo monkey CD8+T cells
*Conclusions: In both humans and monkeys, higher Eomes expression correlates with effector T cell phenotype after allo-stimulation. However, concomitant expression of T-bet and the exhaustion/activation markers CTLA4 and PD-1 was different. The role of Eomes in the development and maintenance of allo-reactive Tmem may not be identical in human and nonhuman primates.
To cite this abstract in AMA style:Gutierrez APerez, Thomson AW, Metes DM, Ezzelarab MB. Phenotypic and Functional Analysis of Non-Activated and Allo-Activated Eomesodermin+ CD8+ T Cells in Humans and Nonhuman Primates [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/phenotypic-and-functional-analysis-of-non-activated-and-allo-activated-eomesodermin-cd8-t-cells-in-humans-and-nonhuman-primates/. Accessed June 15, 2021.
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