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Regulating t helper cell immunity through antigen responsiveness and calcium entry

Academic Article
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Overview

authors

  • Bikah, G.
  • Pogue-Caley, R. R.
  • McHeyzer-Williams, L. J.
  • McHeyzer-Williams, Michael G.

publication date

  • November 2000

journal

  • Nature Immunology  Journal

abstract

  • 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.

subject areas

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

International Standard Serial Number (ISSN)

  • 1529-2908

Digital Object Identifier (DOI)

  • 10.1038/80841

PubMed ID

  • 11062500
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Additional Document Info

start page

  • 402

end page

  • 412

volume

  • 1

issue

  • 5

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