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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.