Calcium signaling mechanisms in T lymphocytes

Annu Rev Immunol. 2001;19:497-521. doi: 10.1146/annurev.immunol.19.1.497.


Elevation of intracellular free Ca(2+) is one of the key triggering signals for T-cell activation by antigen. A remarkable variety of Ca(2+) signals in T cells, ranging from infrequent spikes to sustained oscillations and plateaus, derives from the interactions of multiple Ca(2+) sources and sinks in the cell. Following engagement of the T cell receptor, intracellular channels (IP3 and ryanodine receptors) release Ca(2+) from intracellular stores, and by depleting the stores trigger prolonged Ca(2+) influx through store-operated Ca(2+) (CRAC) channels in the plasma membrane. The amplitude and dynamics of the Ca(2+) signal are shaped by several mechanisms, including K(+) channels and membrane potential, slow modulation of the plasma membrane Ca(2+)-ATPase, and mitochondria that buffer Ca(2+) and prevent the inactivation of CRAC channels. Ca(2+) signals have a number of downstream targets occurring on multiple time scales. At short times, Ca(2+) signals help to stabilize contacts between T cells and antigen-presenting cells through changes in motility and cytoskeletal reorganization. Over periods of minutes to hours, the amplitude, duration, and kinetic signature of Ca(2+) signals increase the efficiency and specificity of gene activation events. The complexity of Ca(2+) signals contains a wealth of information that may help to instruct lymphocytes to choose between alternate fates in response to antigenic stimulation.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen Presentation
  • Calcineurin / physiology
  • Calcium / metabolism
  • Calcium Channels / metabolism
  • Calcium Channels / physiology
  • Calcium Signaling / physiology*
  • Calcium-Transporting ATPases / physiology
  • Cell Compartmentation
  • DNA-Binding Proteins / physiology
  • Endoplasmic Reticulum / metabolism
  • Gene Expression Regulation / physiology
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ion Transport
  • Jurkat Cells
  • Membrane Potentials
  • Mitochondria / physiology
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Patch-Clamp Techniques
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Cytoplasmic and Nuclear / physiology
  • T-Lymphocytes / physiology*
  • Transcription Factors / physiology
  • Transcriptional Activation


  • Calcium Channels
  • DNA-Binding Proteins
  • ITPR1 protein, human
  • Inositol 1,4,5-Trisphosphate Receptors
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Calcineurin
  • Calcium-Transporting ATPases
  • Calcium