Lymphocyte apoptosis induced by Fas ligand-expressing ovarian carcinoma cells: Implications for altered expression of T cell receptor in tumor- associated lymphocytes

Abstract

We have recently reported that tumor-associated lymphocytes obtained from ascitic fluids of women with ovarian carcinoma (OvCA) demonstrate a marked decrease in expression of cytoplasmic CD3-ζ and surface CD3-ε chains, which is associated with altered function of T cell receptor (TcR). We now demonstrate that OvCAs in situ and in culture express functional Fas ligand (FasL), capable of triggering an intrinsic cell death program in Fas- expressing T cells. The possibility of a relationship between cell death and altered expression of TcR was examined. The data indicate that alterations in expression of CD3-ζ and CD3-ε chains in T cells coincubated with OvCA are related to tumor-induced apoptosis, as the addition of pan-caspase inhibitors, DEVD-cho or YVAD-cho, prevents both the in vitro induction of T cell death by OvCA cells and the changes in the level of expression of CD3- ζ and CD3-ε chains. In the presence of Fas-Fc fusion protein, but not Fc- control protein, the loss in expression of CD3-ζ and CD3-ε chains induced in T cells by FasL+ OvCA cells was prevented. These results suggest that the loss in expression of CD3-ζ and CD3-ε chains in T lymphocytes interacting with OvCA cells is associated with apoptosis mediated by FasL-expressing tumor cells.