IL-2 receptor γ chain cytokines differentially regulate human CD8(+)CD127(+) and CD8(+)CD127(−) T cell division and susceptibility to apoptosis

Expression of IL-7 receptor α (CD127) is associated with naive and memory (i.e. non-effector) CD8(+) T cell phenotypes. Effector CD8(+) T cells are predominantly CD127(−) and most die by apoptosis. Therefore, CD127 appears to be a marker for CD8(+) T cell differentiation, yet its role in CD8(+) T cell survival and memory development is unclear. To address this, we investigated the cell death and cell division of isolated CD8(+)CD127(+) and CD8(+)CD127(−) T cells in response to common IL-2 receptor γ chain (γ(C)) cytokines other than IL-7. We show here that (i) memory cells (CD127(+)CD45RA(−)) divide frequently in response to either IL-2, -4 or -15; (ii) IL-2 and -15 enhance cell division in effector–memory-like cells (CD127(−)CD45RA(+)) while IL-4 enhances the cell division of effector cells (CD127(−)CD45RA(−)); (iii) CD8(+)CD127(+) T cells are more sensitive to the anti-apoptotic effects of IL-2 or IL-15 than CD8(+)CD127(−) T cells and (iv) CD8(+)CD127(+) T cell produce more Bcl-2 in response to IL-2 or IL-15 compared with CD8(+)CD127(−) T cells. Therefore, CD8(+)CD127(+) and CD8(+)CD127(−) T cells differ in their responsiveness to cell division and anti-apoptotic signals from IL-2, -4 and -15. This suggests a role for γ(C) cytokines in the pathogenesis of diseases in which CD127 expression is altered on CD8(+) T cells such as in progressive viral infections and cancer.