Date: Tuesday, May 5, 2015
Session Time: 5:30pm-6:30pm
Presentation Time: 5:30pm-6:30pm
Location: Exhibit Hall E
Background. Contradictory observations have been published regarding the functionality of TEMRA CD8 T cells. TEMRA CD8 have been shown to accumulate with age or chronic antigen stimulation and thus to lead to immune-senescence. In contrast, we and others have shown that TEMRA CD8 are involved in a wide array of pathogenic process, including kidney transplant rejection and bone regeneration. We aimed in the present study to assess the functionality and the metabolic profiles of TEMRA CD8 in healthy volunteers and in clinical settings in which CD8 compartments has been shown to undergo strong modifications (kidney transplantation and multiple sclerosis).
Method. Cytokine secretion and proliferation of naïve (CD45RA+CD28+), TEMRA (CD45RA+CD28-), EM early (CD45RA-CD28+) and EM late (CD45RA-CD28-) CD8 T cells were assessed after 2 and 5 days of culture with coated anti-CD3 in combination with IL-2, IL-7 or IL-15. Integrity and polarization of mitochondria were assessed. Mitochondrial Respiration and glycolysis were characterized using Seahorse XF Analyser under basal condition and upon PMA/Ionomycin activation. Finally, glycolysis and mitochondrial respiration were inhibited by 2-DG and metformin respectively, and pro-inflammatory cytokines secretion was assessed upon aCD3aCD28 stimulation.
Results. We first show that TCR stimulation is sufficient to induce TEMRA CD8 cell proliferation and pro-inflammatory cytokine secretion in contrast to naïve CD8. IL-2, IL-7 and IL-15 stimulation results in a rapid phosphorylation of STAT5 in TEMRA CD8 and enhances their proliferation. Immuno-metabolic profile of TEMRA CD8 was then in-depth characterized. In contrast to naïve CD8, resting TEMRA CD8 exhibit a greater amount of ATP that that can be rapidly mobilized upon stimulation. TEMRA CD8 exhibit polarized and functional mitochondria, and switch rapidly to glycolysis upon activation. Finally, we show that glycolysis and not mitochondrial respiration is necessary for pro-inflammatory cytokine secretion by TEMRA CD8 in healthy volunteers and in patients with low or high immune stimulation.
Conclusion. In contrast to their view as senescent cells, we provides evidences that TEMRA CD8 shares similar immuno-metabolic features with effector memory and strengthen the need to re-assess their pathogenic role.
To cite this abstract in AMA style:Yap M, Tilly G, Giral M, Laplaud D-A, Brouard S, Pecqueur C, Degauque N. Rapid Effector Function of TEMRA CD8 T Cells in Healthy Volunteers and in Immune-Stimulated Patients Requires Sustained Glycolytic Switch [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/rapid-effector-function-of-temra-cd8-t-cells-in-healthy-volunteers-and-in-immune-stimulated-patients-requires-sustained-glycolytic-switch/. Accessed September 21, 2021.
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