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Endothelial cell costimulation of T cell activation through CD58-CD2 interactions involves lipid raft aggregation
1Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 10, 2001
Summary
Human endothelial cells (EC) costimulate T cell activation via CD2 interactions, amplifying multiple signaling pathways rather than a single one. This process involves lipid raft aggregation, enhancing T cell receptor signaling.
Area of Science:
- Immunology
- Cellular Biology
Background:
- Human endothelial cells (EC) play a role in T cell activation.
- CD2-CD58 interactions are known costimulatory pathways between EC and T cells.
Purpose of the Study:
- To investigate if EC activate distinct costimulatory pathways targeting specific transcription factors in T cells.
- To elucidate the role of CD2 in EC-mediated T cell costimulation.
Main Methods:
- Analysis of transcription factor activity using reporter genes (AP-1, NF-AT, NF-kappaB, NF-IL-2).
- Assessment of T cell activation and IL-2 secretion.
- Investigation of lipid raft aggregation and the effect of CD2 antibodies.
Main Results:
- EC costimulation up-regulated multiple transcription factor reporters (AP-1, NF-AT, NF-kappaB, NF-IL-2) similarly.
- CD2 monoclonal antibodies (mAbs) blocked EC effects on all tested pathways and IL-2 secretion.
- EC costimulation promoted lipid raft aggregation, enhancing T cell receptor (TCR) signaling upstream of TCR engagement.
Conclusions:
- EC costimulation via CD2 amplifies, rather than uniquely activates, multiple T cell signaling pathways downstream of the TCR.
- CD2 is critical for organizing the T cell-APC contact zone and enhancing TCR signaling through lipid raft aggregation.