The role of CD8 T cell replicative senescence in human aging.

Extract: Normal somatic cells are strictly limited in the number of times they can divide. This intrinsic barrier to unlimited proliferation, a process known as replicative senescence, was first described by Hayflick and colleagues nearly fifty years ago in cell cultures of normal fibroblasts (connective tissue cells), and has since been documented for a variety of human cell types, including epithelial cells (cells which make up the inner and outer surface of vessels, organs, etc.), keratinocytes (cells that produce keratin which becomes hair, skin and nails), endothelial cells (cells that line, for instance, the circulatory system) and hepatocytes (liver cells) cultured in vitro. Ironically, it was only recently that this cell culture model was adapted to the so-called CD8 (cytotoxic) T cell, the immune cell type that is actually required to undergo extensive proliferation in order to function effectively in controlling infections. The reason that clonal expansion is so crucial for proper immune function is that each lymphocyte expresses a unique antigen receptor, i.e., recognizes one specific "substance." During a viral infection, the few T cells that recognize that particular virus must undergo extensive cell division to produce sufficient effector cells to clear the infection. Once an infection is cleared, most of the CD8 T cells die by apoptosis (programmed cell death), leaving just a few memory cells with the same antigen receptor to deal with possible future encounters with the same pathogen, at which time the process of clonal expansion is repeated.