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 protect ed T cell hybridomas from activation-induced cell death. The protection app ears 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 in to two subsets based on the level of CD43 surface expression. The CD4(+)CD4 3(low) subset exhibits a naive T cell phenotype, being CD62L(high)CD45RB(hi gh)CD44(low), whereas CD4(+)CD43(high) cells exhibit a memory phenotype, be ing 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 cell s. We confirm here that peripheral CD4(+)CD43(high) T cells are resistant t o TCR/CD3-mediated cell death. These results suggest that the expression le vels of CD43 on naive and memory CD4(+) T cells determine their susceptibil ity 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 pro vides a novel mechanism by which tumor cells expressing abnormally high lev els of CD43 may escape Fas-mediated killing.