Regulating T helper cell immunity through antigen responsiveness and calcium entry

Nat Immunol. 2000 Nov;1(5):402-12. doi: 10.1038/80841.


We evaluated changes in the signaling potentials and proliferative capacity of single antigen-specific T helper (TH) cells during a primary immune response to a protein antigen. At the peak of cellular expansion in vivo all antigen-specific TH cells exhibited a profound block in CD3- and CD4-mediated mobilization of intracellular calcium together with a more global block in T cell receptor-independent capacitative calcium entry (CCE). The proliferative response of these antigen-specific TH cells to anti-CD3, anti-CD28 and IL-2 was also severely blunted. Cross-linking CD69 on a substantial fraction of CD69+ antigen-specific TH cells relieved this block in CCE and restored proliferative capacity in vitro. The CCE rescue operated through a CD69-coupled G protein and required calcium-bound calmodulin and calcineurin. These data reveal critical changes in the responsiveness of antigen-specific TH cells and provide evidence of new mechanisms for the regulation of antigen-specific TH cell development in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens / administration & dosage*
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD28 Antigens / metabolism
  • CD3 Complex / metabolism
  • CD4 Antigens / metabolism
  • Calcineurin / metabolism
  • Calcium Signaling*
  • Calmodulin / metabolism
  • Cell Division
  • Columbidae
  • Cross-Linking Reagents
  • Cytochrome c Group / immunology
  • GTP-Binding Proteins / metabolism
  • In Vitro Techniques
  • Lectins, C-Type
  • Lymphocyte Activation
  • Mice
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism*


  • Antigens
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD28 Antigens
  • CD3 Complex
  • CD4 Antigens
  • CD69 antigen
  • Calmodulin
  • Cross-Linking Reagents
  • Cytochrome c Group
  • Lectins, C-Type
  • Receptors, Antigen, T-Cell
  • Calcineurin
  • GTP-Binding Proteins