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Autocrine T-cell suicide mediated by APO-1/(Fas/CD95)
Nature
|February 2, 1995
Summary
T-cell receptor activation triggers APO-1 (also known as Fas/CD95) mediated apoptosis in human T cells. This pathway, involving APO-1 ligand, explains T-cell deletion and immune response regulation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- The APO-1/(Fas/CD95) receptor, part of the TNF receptor superfamily, mediates programmed cell death (apoptosis).
- Activated T cells (ATC) from lpr/lpr mice show defective T-cell receptor (TCR)-induced apoptosis, suggesting APO-1's role.
Purpose of the Study:
- To investigate the involvement of the APO-1 receptor in TCR-induced apoptosis in human T cells.
- To elucidate the mechanism of TCR-induced apoptosis and its regulation.
Main Methods:
- Utilized malignant Jurkat cells, an alloreactive T-cell clone (S13), and peripheral ATC.
- Triggered TCR signaling using immobilized anti-CD3 antibodies and Staphylococcus enterotoxin B (SEB).
- Assessed apoptosis inhibition using anti-APO-1 antibody fragments and soluble APO-1 receptor decoys.
Main Results:
- TCR triggering induced APO-1 ligand expression and apoptosis in all tested human T cells.
- Apoptosis was significantly inhibited by blocking APO-1 interactions.
- A soluble APO-1 ligand was detected in the supernatant of activated Jurkat cells.
Conclusions:
- TCR-induced apoptosis in ATC can occur via APO-1 ligand-mediated autocrine signaling (suicide).
- This mechanism contributes to immune response suppression and peripheral tolerance through T-cell deletion.