Apoptosis induced in T cells by human neuroblastoma cells: role of Fas ligand.
The CD95/CD95L (Fas/Fas ligand) receptor/ligand system plays an important role in regulation of cell survival and induction of a programmed cell death. It is also involved in regulation of effector phase of T and NK cell cytotoxicity, establishment of immune privilege sites, and tumor escape from immune recognition. In this study, we assessed expression of CD95L in tumors obtained from patients with neuroblastoma (NB) and in established NB cell lines. We measured the presence of intratumoral T cell infiltrates and T cell survival in tumor tissue samples. High levels of apoptosis were observed in tumor-associated lymphocytes as well as in Jurkat T cells cocultured with NB cells in vitro. T cell death was reduced after treatment of NB cells (in vitro) with antibody to FAS ligand (FasL). Overall, our data suggest that NB-induced apoptosis of Fas-sensitive Jurkat T cells is mediated by functional FasL expressed on NB and Fas/FasL interaction may be responsible for the elimination of T cells in the NB microenvironment.
Shurin
G V
GV
University of Pittsburgh Cancer Institute, Division of Pediatric Surgery, Children's Hospital of Pittsburgh, PA 15213, USA.
Gerein
V
V
Lotze
M T
MT
Barksdale
E M
EM
D017209:Apoptosis / Q000276:immunology*; D001483:Base Sequence; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers / Q000235:genetics; D053222:Fas Ligand Protein; D015870:Gene Expression; D006801:Humans; D019169:Jurkat Cells; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
D017931:DNA Primers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019014:fas Receptor