Lymphocyte apoptosis induced by Fas ligand- expressing ovarian carcinoma cells. Implications for altered expression of T cell receptor in tumor-associated lymphocytes.
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-zeta and surface CD3-epsilon 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-zeta and CD3-epsilon 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-zeta and CD3-epsilon chains. In the presence of Fas-Fc fusion protein, but not Fc-control protein, the loss in expression of CD3-zeta and CD3-epsilon chains induced in T cells by FasL+ OvCA cells was prevented. These results suggest that the loss in expression of CD3-zeta and CD3-epsilon chains in T lymphocytes interacting with OvCA cells is associated with apoptosis mediated by FasL-expressing tumor cells.
Rabinowich
H
H
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA. rabinow+@pitt.edu
Reichert
T E
TE
Kashii
Y
Y
Gastman
B R
BR
Bell
M C
MC
Whiteside
T L
TL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D017252:CD3 Complex / Q000032:analysis*; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D019014:fas Receptor / Q000032:analysis
D017252:CD3 Complex; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor