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Table 1 Impact of age-associated signalling changes

From: Immunity, ageing and cancer

Features altered Resulting altered mechanism
Cholesterol level Signalling molecule recruitment [135]
Membrane fluidity Protein interaction [54]
Lipid raft functions Early signalling/immune synapse formation [135]
Calcium influx Induction of T cell activation
Phosphatase activity Control of negative signalling
PTK (Lck) activity Phosphorylation of LAT [57, 135]
LAT phosphorylation Activation of LAT-associated molecules
MAP Kinase activation Cellular activation/survival [57, 135]
Cytoskeleton rearrangement Cell-cell contact/Immune synapse formation
Translocation of transcription factors Induction of gene expression
CD28 expression T cell costimulation/anti-apoptotic signals [58]
KIR expression Formation of an activation platform
KLRG-1, CD57, PD-1 expression Induction of T cell activation [92, 158]
  1. For activation, T cells require sustained physical contact with APC. This feature is altered with age due to changes in the integrity of the membrane. Several signalling molecules fail to be activated with age, including PTK and adaptor proteins such as LAT. Calcium metabolism is altered, partly due to impaired PLCγ-1 phosphorylation. The alterations including lipid raft functions influence MAP Kinase activation and cytoskeletal rearrangements, together leading to differential activation and translocation of transcription factors such as NF-κB, NF-AT and AP-1 into the nucleus. This directly affects T cell clonal expansion due to decreased IL-2 production. Unbalanced negative signalling involving inhibitory receptors such as KIR2DL2 or Natural Killer Receptors contribute to reduce activation. PTK: protein tyrosine kinase; LAT: linker for activation of T cells; MAPK: Mitogen activated protein kinase; KIR: inhibitory killer immunoglobulin-like receptors; PLCγ-1: Phospholipase C-gamma 1.