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^highCD45RB^highCD44^low, whereas CD4⁺CD43^high cells exhibit a memory phenotype, being CD62L^lowCD45RB^lowCD44^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.