High level expression of CD43 inhibits T cell receptor/CD3-mediated apoptosis.
In a screen designed to identify genes that regulate T cell receptor (TCR)/CD3-mediated apoptosis, we found that high level expression of CD43 protected T cell hybridomas from activation-induced cell death. The protection appears to result from its capacity to block Fas-mediated death signals rather than from inhibition of the upregulation of Fas and/or Fas ligand after T cell stimulation. We found that peripheral CD4(+) T cells can be divided into two subsets based on the level of CD43 surface expression. The CD4(+)CD43(low) subset exhibits a naive T cell phenotype, being CD62L(high)CD45RB(high)CD44(low), whereas CD4(+)CD43(high) cells exhibit a memory phenotype, being CD62L(low)CD45RB(low)CD44(high). Recent studies have demonstrated that engagement of TCR and Fas induces naive CD4(+) T cells to undergo apoptosis, and the same treatment enhances the proliferation of memory CD4(+) T cells. We confirm here that peripheral CD4(+)CD43(high) T cells are resistant to TCR/CD3-mediated cell death. These results suggest that the expression levels of CD43 on naive and memory CD4(+) T cells determine their susceptibility to Fas-dependent cell death and that high level expression of CD43 may be used as a marker to define CD4(+) memory T cells. Expression of CD43 provides a novel mechanism by which tumor cells expressing abnormally high levels of CD43 may escape Fas-mediated killing.
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Related Subject Headings
- fas Receptor
- Signal Transduction
- Sialoglycoproteins
- Receptors, Antigen, T-Cell
- Mice
- Leukosialin
- Immunology
- Hybridomas
- CD4-Positive T-Lymphocytes
- Apoptosis
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- fas Receptor
- Signal Transduction
- Sialoglycoproteins
- Receptors, Antigen, T-Cell
- Mice
- Leukosialin
- Immunology
- Hybridomas
- CD4-Positive T-Lymphocytes
- Apoptosis