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ICAM-3 (CD50) cross-linking augments signaling in CD3-activated peripheral human T lymphocytes
S M Berney1, T Schaan, J S Alexander
1Department of Medicine, Center of Excellence for Arthritis and Rheumatology, Louisiana State University School of Medicine at Shreveport, 71130-3932, USA. sberne@lsumc.edu
Journal of Leukocyte Biology
|June 25, 1999
Summary
Intercellular Adhesion Molecule 3 (ICAM-3) acts as a costimulatory molecule for resting T cells. Signaling through ICAM-3 enhances T cell activation by augmenting CD3 signaling, crucial for immune responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Signaling
Background:
- ICAM-3 is a constitutive adhesion molecule found on hematopoietic cells.
- It typically binds LFA-1 on antigen-presenting cells (APC), stabilizing T cell-APC interactions and facilitating CD3/TCR signaling.
- Emerging evidence suggests ICAM-3 may also play a direct role in T cell signaling.
Purpose of the Study:
- To investigate the potential signaling function of ICAM-3 in resting human T cells.
- To determine if ICAM-3 acts as a costimulatory molecule during initial T cell activation.
Main Methods:
- Purified resting human T cells were stimulated using plate-bound antibodies to cross-link ICAM-3 and CD3.
- Assessed changes in cell size (blastogenesis), surface marker expression (CD25, CD69), and T cell metabolism.
- Measured phosphatidylinositol hydrolysis and phospholipase C-gamma1 phosphorylation.
Main Results:
- Co-crosslinking ICAM-3 and CD3 led to increased cell size, blastogenesis, and synergistic upregulation of CD25 and CD69.
- T cell metabolism was significantly enhanced.
- Concomitant stimulation increased phosphatidylinositol hydrolysis and phospholipase C-gamma1 phosphorylation in resting T cells.
Conclusions:
- ICAM-3 augments CD3 signaling in resting human T cells.
- ICAM-3 functions as a costimulatory molecule, enhancing the initial activation step of T cells.
- These findings highlight a novel role for ICAM-3 in T cell activation pathways.