Replicative senescence and shifts in gene expression. Cumulative replication of T cells is associated with telomeric erosion and loss of CD28 and CD40L expression, consistent with cellular senescence. Presenescent CD4+ T cells gain effector functions such as high production of cytokines and cytotoxic ability through a perforin/granzyme mechanism. These cells are under the regulatory control of MHC class I-recognizing receptors, such as killer immunoglobulin-like receptors (KIRs), that can provide costimulatory signals or, if coexpressed with the appropriate adapter molecule DAP12, form an independent, fully competent recognition unit.
Goronzy and Weyand Arthritis Res Ther 2003 5:225-234 doi:10.1186/ar974