title: The potency of TCR signaling differentially regulates NFATc/p activity and early IL-4 transcription in naive CD4+ T cells.
abstract: The potency of TCR signaling can regulate the differentiation of naive CD4(+) T cells into Th1 and Th2 subsets. In this work we demonstrate that TCR signaling by low-affinity, but not high-affinity, peptide ligands selectively induces IL-4 transcription within 48 h of priming naive CD4(+) T cells. This early IL-4 transcription is STAT6 independent and occurs before an increase in GATA-3. Furthermore, the strength of the TCR signal differentially affects the balance of NFATp and NFATc DNA binding activity, thereby regulating IL-4 transcription. Low-potency TCR signals result in high levels of nuclear NFATc and low levels of NFATp, which are permissive for IL-4 transcription. These data provide a model for how the strength of TCR signaling can influence the generation of Th1 and Th2 cells.
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Brogdon
authors.forename: David
authors.initials: D
authors.lastname: Leitenberg
authors.forename: Kim
authors.initials: K
authors.lastname: Bottomly
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003574:Cytochrome c Group / Q000138:chemical synthesis / Q000378:metabolism / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004306:Dose-Response Relationship, Immunologic; D015847:Interleukin-4 / Q000235:genetics*; D007399:Interphase / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009036:Moths; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism / Q000502:physiology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D003574:Cytochrome c Group; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C494007:Nfatc2 protein, mouse; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D015847:Interleukin-4; D002118:Calcium