The Potency of TCR Signaling Differentially Regulates NFATc/p Activity and Early IL-4 Transcription in Naive CD4+ T Cells

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. T...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2002-04, Vol.168 (8), p.3825-3832
Main Authors: Brogdon, Jennifer L, Leitenberg, David, Bottomly, Kim
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Calcium - metabolism
Cytochrome c Group - chemical synthesis
Cytochrome c Group - metabolism
Cytochrome c Group - physiology
DNA-Binding Proteins - metabolism
Dose-Response Relationship, Immunologic
Interleukin-4 - genetics
Interphase - genetics
Interphase - immunology
Mice
Mice, Inbred A
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
Moths
NFATC Transcription Factors
Nuclear Proteins
Peptide Fragments - chemical synthesis
Peptide Fragments - metabolism
Peptide Fragments - physiology
Protein Binding - genetics
Protein Binding - immunology
Receptors, Antigen, T-Cell - metabolism
Receptors, Antigen, T-Cell - physiology
Signal Transduction - genetics
Signal Transduction - immunology
T-Lymphocyte Subsets - cytology
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
Transcription Factors - metabolism
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.168.8.3825