FASEB Journal · Nov 1, 2018
CD8⁺, but not CD4⁺ effector/memory T cells, express the CD44highCD45RBhigh phenotype with aging, which displays reduced expression levels of P2X₇ receptor and ATP-induced cellular responses
By Mellouk A, Bobé P
Previously we reported that the sensitivity of CD4⁺ T cells to ATP does not depend on P2X₇ receptor (P2X₇R) expression levels but on their activation and differentiation stages. Therefore, here we have investigated a potential relationship between the sensitivity of CD8⁺ T cells to ATP and their stages of differentiation. Thus, the CD8⁺ subpopulation exhibits a drastically reduced sensitivity to ATP with aging, which parallels the strong increase of an effector/memory CD8⁺ subset expressing high levels of CD44 cell adhesion molecule and CD45RB transmembrane phosphatase (CD44hiCD45RBhi). Using l-selectin/CD62L, CC-chemokine receptor 7, and CD127/IL-7 receptor-α markers, we showed that effector/memory CD8⁺ T cells belong to a central or effector memory subset. In contrast, the CD44hiCD45RBhi effector/memory subset is absent or poorly expressed in the CD4⁺ T subpopulation regardless of age. While ATP treatment can trigger channel and pore formation, CD62L shedding, phosphatidylserine exposure, and cell death in the CD44loCD45RBhi-naive CD8⁺ subset, it is unable to induce these cellular activities in the CD44hiCD45RBhi effector/memory CD8⁺ subset. Importantly, both CD44loCD45RBhi-naive and CD44hiCD45RBhi effector/memory subsets express similar low levels of P2X₇R, demonstrating that the sensitivity of CD8⁺ T cells to ATP depends on the stage of differentiation instead of P2X₇R expression levels.-Mellouk, A., Bobé, P. CD8⁺, but not CD4⁺ effector/memory T cells, express the CD44highCD45RBhigh phenotype with aging, which displays reduced expression levels of P2X₇ receptor and ATP-induced cellular responses.