Session Name: Innate Immunity; Chemokines, Cytokines, Complement
Session Date & Time: None. Available on demand.
*Purpose: Human CD4+CD8loT cells have been reported in patients with organ allograft rejection. We evaluated the incidence, phenotype, and function of CD4+CD8loT cells in nonhuman primates (NHP).
*Methods: Peripheral blood mononuclear cells (PBMC) were isolated from peripheral blood of naïve rhesus monkeys. The percentages of CD4+CD8loT cells were evaluated. In comparison to CD4+CD8negT cells, memory T cell (Tmem) subsets were evaluated based on their expression of CD45RA, CCR7, CD28, and CD95. Effector function was assessed by the production of interferon-gamma (IFNg) and tumor necrosis factor-alpha (TNFa). Cytokine production was also assessed after stimulation with allogeneic PBMC for 5 days. The mean fluorescence intensity (MFI) of T-box transcription factors T-bet and Eomesodermin (Eomes) was also assessed.
*Results: In naïve rhesus monkeys, the percentage of CD4+CD8loT cells in peripheral blood was 1.54±0.32%. In CD4+CD8loT cells, CD45RA–CCR7– effector Tmem (Tem) were 17.9±2.0%, compared to 11.3±1.1% in CD4+CD8negT cells (p<0.01). CD45RA+CCR7– terminally-differentiaed effector Tmem (Temra) were 25.3±4.2%, compared to 5.8±0.8% in CD4+CD8neg T cells (p<0.01). CD95+CD28– Tem were 33.4±5.5%, compared to 4.0±0.8% in CD4+CD8negT cells (p<0.01).The percentage of IFNg+TNFa+ T cells in CD4+CD8loT cells was 28.6±3.1%, compared to 8.2±1.8% in CD4+CD8neg T cells (p<0.01) Notably, following allogeneic stimulation, IFNg+TNFa+ T cells were significantly higher in CD4+CD8loT cells (22.7±3.3%) compared to CD4+CD8negT cells (8.7±0.8%) (p<0.01). Additionally, CD4+CD8loT cells exhibited significantly higher Eomes and T-bet expression (MFI= 95.6±3.7 and 588.7±87, respectively), compared to CD4+CD8negT cells (MFI= 66.1±3.2, and 232.3±3.5, respectively) (p<0.05).
*Conclusions: We show for the first time that under steady-state conditions, CD4+CD8loT cells exhibit a higher memory profile and effector function in comparison to CD4+CD8negT cells. These findings justify the evaluation of the role of CD4+CD8loT cells in organ allograft rejection in NHP and their response to therapeutic intervention.
To cite this abstract in AMA style:Kubo M, Sasaki K, Gutiérrez AP, Lu L, Vujevich V, Thomson AW, Ezzelarab M. Naïve Rhesus Monkey CD4+CD8loT Cells Comprise High Percentage of Memory T Cells with Strong Effector Function [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/naive-rhesus-monkey-cd4cd8lot-cells-comprise-high-percentage-of-memory-t-cells-with-strong-effector-function/. Accessed June 16, 2021.
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