CD28 signals in the immature immunological synapse

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.