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High Level Expression of CD43 Inhibits T Cell Receptor/CD3-mediated Apoptosis

High Level Expression of CD43 Inhibits T Cell Receptor/CD3-mediated Apoptosis,Michael J. Bevan

High Level Expression of CD43 Inhibits T Cell Receptor/CD3-mediated Apoptosis   (Citations: 19)
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Summary In a screen designed to identify genes that regulate T cell receptor (TCR)/CD3-mediated apop- tosis, 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 1 T cells can be divided into two subsets based on the level of CD43 surface expression. The CD4 1 CD43 low subset exhibits a naive T cell phenotype, being CD62L high CD45RB high CD44 low , whereas CD4 1 CD43 high cells exhibit a mem- ory phenotype, being CD62L low CD45RB low CD44 high . Recent studies have demonstrated that engagement of TCR and Fas induces naive CD4 1 T cells to undergo apoptosis, and the same treatment enhances the proliferation of memory CD4 1 T cells. We confirm here that periph- eral CD4 1 CD43 high T cells are resistant to TCR/CD3-mediated cell death. These results sug- gest that the expression levels of CD43 on naive and memory CD4 1 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 1 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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