Signal transduction in the aging immune system

T cells from aged mice show defects in the early stages of the activation process, including alterations in cytoskeletal reorganization that precede discrimination, by the T cell receptor, of agonist from antagonist peptides. Aging also modifies the pattern of glycosylation of T cell surface macromolecules, and enzymatic cleavage of these modified glycoproteins can restore high level responses to T cells from aged mice. Alterations in plasma membrane lipids and cholesterol-rich microdomains might also contribute to age-related deficits in T cell signaling. Evidence for intrinsic signal defects in aged B cells is more limited, but might involve pathways that activate the transcription factor E47, which has been implicated in somatic hypermutation and class-switch recombination.