Previous findings including ours have suggested that in chronic HD patients, a significantly high percentage of activated CD4+ T cells ultimately do not proliferate but become apoptotic. The induction of activated CD4+ T cell apoptosis from HD patients was dependent on Fas/FasL expression, which leads to a cell contact form of circulating CD4+ T cell self-injury. Furthermore, the investigators showed that activated CD4+ T cells from these patients fail to respond adequately to exogenous IL-2. This is due to the downmodulation of surface IL-2 receptor (IL-2R) beta and gamma subunit expression, impaired IL-2 signal transduction in CD4+ T cells, and/or increased serum levels of soluble IL-2R (sIL-2R). Moreover, in vivo sensitization to IL-2 or low synthesis of endogenous IL-2, themselves potentially may lead to enhanced sensitivity to T cell apoptosis. Decreased proliferative capacity of CD69+/CD4+ T cells that were from individuals with normal renal function and incubated with serum from chronic HD patients and its restoration by normal serum strongly suggest that mediators that are induced by HD affect transduction mechanisms in the IL-2/IL-2R pathway. Finally, IL-2 seems to inhibit the apoptotic process at many stages by interacting with various proteins. Therefore, the investigators postulated that, in HD patients, oxidative stress that is induced by oxLDL may increase CD4+ T cell sensitivity to Fas-mediated apoptosis, in part as a consequence of an HD patient's specific dysregulation of IL-2 expression. To test this hypothesis, the investigators assessed the role of Fas and IL-2 in mediating the oxLDL-induced CD4+ T cell dysfunction in patients with ESRD.