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.
He
Y W
YW
Department of Immunology, Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.
Bevan
M J
MJ
D000818:Animals; D015703:Antigens, CD; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D006825:Hybridomas; D051917:Leukosialin; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012795:Sialoglycoproteins / Q000096:biosynthesis / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
D015703:Antigens, CD; D051917:Leukosialin; D011948:Receptors, Antigen, T-Cell; D012795:Sialoglycoproteins; C497863:Spn protein, mouse; D019014:fas Receptor