Change And Regulation Mechanism Of Cd28 In Immune Aging

In 1956, Denham Harman first articulated the 'free radical theory' of aging, speculating that endogenous ROS were generated in cells and causing cumulative damage (Harman, 1957). Now, many kinds ROS have been found, including superoxide, H2O2, nitric oxide (NO), and hydroxyl radicals. These various radical species can either be generated exogenously or produced intracellularly from different ways, they have been recognized to regulate many important cellular events including gene expression (Lo and Cruz, 1995), transcription factor activation (Schreck et al., 1991), and cellular proliferation (Murrell et al., 1990).Among many consequences of aging, a main factor is the progressive decline in protective immunity. The incidence of malignancies increases with age, and aging people have increased susceptibility to infections and blunted responses to vaccines. Although the molecular mechanisms of immunosenescence are not yet clear, the loss of effective immune activity is largely due to alterations within T cells.With advancing age, substantial changes in both the functional and phenotypic profiles of T cells have been reported and reviewed (Pawelec et al., 2001; L. Ginaldi et al., 1999). One of important changes in the phenotypic CD4⁺ T cell profiles is decreased expression of CD28 and the advent of a subgroup of CD28^null cells (Caruso et al., 1996; Vallejo et al., 1998). CD28 is a major costimulatory molecule in the generation of T cell-mediated immune responses (Ward,1996; Lenschow et al., 1996). Ligation of CD28 promotes proliferation and cytokine production follow antigen engagement (Jenkins et al., 1991).Put together, we think that expression of CD28 declined and oxidants accumulated in the elderly. It may have important consequences to study the regulation of CD28-expression under oxidative stress during immunosenescence.In order to explore these questions, we made a research design from three aspects and obtained significant results as follows:...