PSGL-1引發活化T細胞死亡之分子機制探討
Molecular Mechanisms of P-selectin Glycoprotein Ligand-1-Mediated Cell Death in Activated T Cells
Date Issued
2004
Date
2004
Author(s)
Chen, Shu-Ching
DOI
en-US
Abstract
Abstract
The immune system evolves several sophisticated strategies to regulate immune responses. In general, contact with their specific antigen causes naïve T cells to proliferate and differentiate into effector cells. After the pathogen is destroyed, most effector T cells are eliminated, thereby preserving the size of T cell repertoire. During each stage of this process, the fate of life or death of T cells is strictly regulated.
For many years, the importance of death receptors such as Fas and other TNF receptor family members as well as depiction of death signaling pathway have been emphasized in regulation of activated T cells. In recent years, however, increasing evidence has shown that molecules other than death receptors can also trigger T-cell death. Inhibition of classical caspases can not always prevent T cell death. These observations indicate that death signaling in activated T cells is regulated in a very complicated way.
In order to address the death mechanisms of activated T cells, panels of hamster monoclonal antibodies against mouse activated T cells were generated in our laboratory. Those antibodies with death-triggering function on mouse activated T cells were screened. The most significant one, named TAB4, was found to recognize P-selectin glycoprotein ligand-1 (PSGL-1) or CD162.
PSGL-1 is well known for mediating leukocyte trafficking by interaction with selectins during inflammatory responses. Using the anti-PSGL-1 monoclonal antibody, TAB4, here we demonstrate for the first time that cross-linking of PSGL-1 can trigger a death signal in activated T cells. In contrast to classical cell death, PSGL-1-mediated T cell death is caspase-independent. It involves translocation of apoptosis-inducing factor from mitochondria to nucleus as well as mitochondrial cytochrome c release. Ultrastructurally, both peripheral condensation of chromatin and apoptotic body were observed in PSGL-1-mediated T-cell death. In present study, immobilized P- or E- selectin is also demonstrate to have death-triggering effect on activated T cells. Collectively, this study demonstrates a novel role of PSGL-1 in controlling activated T-cell death and thus advances our understanding of immune regulation.
Our intent in this study is to clarify the molecular mechanisms that determine death of activated T cells and to indicate how these can be integrated into a more complete description of the T cell homeostasis.
Subjects
T細胞死亡
P-selectin Glycoprotein Ligand-1, T cell death
Type
other