Apoptosis-resistant T cells have a deficiency in NF-kappaB-mediated induction of Fas ligand transcription.
Apoptosis induced through the TCR in CD4+ T cells is mostly mediated by the inducible expression of Fas ligand (FasL) as a primary event leading to the commitment to death. To gain a better understanding of the transcriptional events that regulate this expression, we took advantage of our previously described mutant Jurkat cells. These cells are deficient in FasL expression and apoptosis induced upon TCR triggering, although their cytokine (IL-2 and IFN-gamma) production is normal. Here we show that both a FasL- and a consensus NF-kappaB-reporter construct are inefficiently induced in these cells compared to wild-type cells. In addition, we demonstrate that the inducible transcriptional activity of the FasL reporter is abolished by specific inhibitors of NF-kappaB activation. Thus, we could trace the deficit of the mutant cells to an inefficient NF-kappaB activation, evidencing a relevant role for NF-kappaB in the regulation of FasL expression in activated T cells. Furthermore, our results suggest that the induction of FasL versus cytokine gene expression is differentially sensitive to NF-kappaB deprivation.
Teixeiro
E
E
Department of Immunology, Fundación Jiménez Díaz, Universidad Complutense, Madrid, Spain.
García-Sahuquillo
A
A
Alarcón
B
B
Bragado
R
R
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D020672:I-kappa B Proteins; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D012333:RNA, Messenger; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D020672:I-kappa B Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C000606204:NFKBIA protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha