Differential sensitivity of naïve and memory subsets of human CD8+ T cells to TNF-alpha-induced apoptosis.

In this investigation, we have examined the relative sensitivity of human naïve, central memory (T(CM)), and two types of effector memory CD8+ T cells (T(EM) and T(EMRA)) to TNF-alpha-induced apoptosis. Our data show that naïve and T(CM) CD8+ T cells were sensitive, whereas T(EM) and T(EMRA) CD8+ T cells were relatively resistant to TNF-alpha-induced apoptosis. The apoptosis profile correlated with the activation of caspase-8 and caspase-3. However, no correlation was observed between relative sensitivity of four CD8+ T cell subsets to apoptosis and the expression of TNFR-I or TNFR-II. T(EM) and T(EMRA) CD8+ T cells displayed increased phosphorylation of IKKalpha/beta and IkappaB and increased NF-kappaB activity as compared to naïve and T(CM) CD8+ T cells. Bcl-2, Bcl-x(L) and FLIP(L) expression was higher and Bax expression was lower in T(EM) and T(EMRA) CD8+ T cells as compared to naïve and T(CM) CD8+ T cells. These data suggest that signaling molecules downstream of TNFRs may be responsible for differential sensitivity among subsets of CD8+ T cells to TNF-alpha-induced apoptosis.