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CD28 signals in the immature immunological synapse

Pietro G Andres1, Kimberly C Howland, Douglas Dresnek

  • 1Department of Pathology, and Division of Gastroenterology, University of California, San Francisco, CA 93143, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|May 7, 2004
PubMed

Insights

CD28 costimulation functions in the immunological synapse before central supramolecular activation complex (c-SMAC) formation. This finding reveals CD28’s crucial role in early T cell activation and synapse development.

Area of Science:

  • Immunology
  • Cellular Biology
  • T cell immunology

Background:

  • T cell activation requires T cell receptor (TCR) signaling and costimulatory signals, primarily from CD28 for naive T cells.
  • The precise timing of CD28 signaling relative to immunological synapse formation, specifically the central supramolecular activation complex (c-SMAC), remains unclear.

Purpose of the Study:

  • To investigate the kinetics of CD28 localization and function in relation to c-SMAC formation during T cell activation.
  • To elucidate the role of CD28 in the early stages of immunological synapse development.

Main Methods:

  • Utilized single-cell recording approaches with CD28-deficient and reconstituted murine T cells.
  • Assessed the kinetics of CD28 localization and its functional impact on calcium signaling and synapse formation.

Main Results:

  • CD28 accumulates at the immature immunological synapse concurrently with TCR and calcium signaling onset.
  • CD28 signaling regulates T cell activation within seconds of TCR-mediated calcium flux.
  • CD28 influences both the initiation and stabilization of the immunological synapse, paralleling its effects on T cell proliferation.

Conclusions:

  • CD28 plays a critical role in the immunological synapse prior to the establishment of the c-SMAC.
  • These findings highlight CD28's involvement in the early, dynamic phases of T cell activation and synapse maturation.

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