Nuclear factor kappaB is required for peptide antigen-induced differentiation of a CD4+CD8+ thymocyte line.
NF-kappaB transcription factors are known to regulate the expression of a number of genes involved in T cell activation and function. Some evidence has suggested that they also play a role in T cell development. However, the role of NF-kappaB in Ag-induced thymocyte differentiation has not been directly addressed to date. Here we critically examine this role by employing DPK, a CD4+CD8+ thymocyte line that undergoes differentiation upon TCR engagement in a process that closely mimics positive selection. Expression of a degradation-resistant form of IkappaBalpha in DPK cells results in constitutive inhibition of NF-kappaB activity. We find that in the absence of NF-kappaB activity, MHC-peptide-induced differentiation of DPK is blocked. Furthermore, differentiation induced by a nonphysiologic stimulus, anti-TCR Ab, is greatly reduced. Altogether, our data indicate a requirement for NF-kappaB in the developmental changes associated with positive selection.
Ochoa-Garay
J
J
Laboratory of Molecular Structure, National Institute of Allergy and Infectious Diseases, Rockville, MD 20852, USA.
Kaye
J
J
Coligan
J E
JE
D000818:Animals; D000941:Antigens; D017209:Apoptosis; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D010856:Columbidae; D003574:Cytochrome c Group / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins; D051379:Mice; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D015345:Oligonucleotide Probes / Q000235:genetics; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors; D014161:Transduction, Genetic
D000941:Antigens; D003574:Cytochrome c Group; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D015345:Oligonucleotide Probes; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D000072000:NF-KappaB Inhibitor alpha