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

Previously we reported that the sensitivity of CD4(+) T cells to ATP does not depend on P2X(7) receptor (P2X(7)R) 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 (CD44(hi)CD45RB(hi)). Using l-selectin/CD62L, CC-chemokine receptor 7, and CD127/IL-7 receptor- markers, we showed that effector/memory CD8(+) T cells belong to a central or effector memory subset. In contrast, the CD44(hi)CD45RB(hi) 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 CD44(lo)CD45RB(hi)-naive CD8(+) subset, it is unable to induce these cellular activities in the CD44(hi)CD45RB(hi) effector/memory CD8(+) subset. Importantly, both CD44(lo)CD45RB(hi)-naive and CD44(hi)CD45RB(hi) effector/memory subsets express similar low levels of P2X(7)R, demonstrating that the sensitivity of CD8(+) T cells to ATP depends on the stage of differentiation instead of P2X(7)R expression levels.Mellouk, A., Bobe, P. CD8(+), but not CD4(+) effector/memory T cells, express the CD44(high)CD45RB(high) phenotype with aging, which displays reduced expression levels of P2X(7) receptor and ATP-induced cellular responses.