Central memory and effector memory subsets of human CD4+ and CD8+ T cells display differential sensitivity to TNF-α-induced apoptosis

Upon activation by antigen, naive T cell subsets undergo proliferation and differentiation into effector cells, followed by the generation of a pool of memory T cells. Based upon migration pattern and functions, they are classified into central memory (predominantly homing to the lymph nodes) and effector memory (predominantly homing to extralymphoid sites) subsets. These subsets are defined phenotypically by a set of cell surface molecules. In this investigation, we demonstrate that naive and central memory CD4+ and CD8+ T cells in humans undergo tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis, whereas effector memory CD4+ and CD8+ T cells are relatively resistant to TNF-alpha-induced apoptosis. We also provide evidence for the molecular mechanisms underlying the differential sensitivity of naive and different sets of memory T cells to TNF-alpha-induced apoptosis.