Proceedings of the National Academy of Sciences · 1985 · 276 citations · 23 references
Life SciencesImmunologyMolecular BiologyGene ExpressionSignal TransductionTranscriptional RegulationCytokine BiologyCytokine RegulationImmune Gene RegulationImmune RegulationT Cell ActivationT Cell BiologyCytokine Expression RegulationCytokine Receptor ExpressionInterleukin RegulationLymphocyte Activation SignalingReceptor-mediated TranscriptionReceptorsT-cell Activation By CytokinesT-cell Dependent Immune Responses
We demonstrate that purified interleukin 2 (IL-2) can directly upregulate IL-2 receptor expression on phytohemagglutinin-activated T lymphocytes maintained in culture until IL-2 receptor expression had markedly declined. The IL-2-induced increase in IL-2 receptor number is maximal within 12 hr, requires new RNA and protein synthesis, and is mediated by an interaction of ligand with the high-affinity receptors for IL-2. IL-2 stimulation results in increased accumulation of IL-2 receptor mRNA within 4 hr, while an increase in IL-2 receptor gene transcription is detected within 30 min in isolated nuclei. In addition, IL-2 incubation results in increased amounts of c-myc and transferrin receptor mRNA, but it does not augment levels of mRNA encoding the beta chain of the T-cell receptor for antigen. These results demonstrate that IL-2 can directly upregulate transcription and expression of its own receptor and, therefore, indicate that IL-2 may regulate IL-2-dependent immune responses, in part, by influencing the expression of IL-2 receptors.
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Takashi Uchiyama, S Broder, Thomas A. Waldmann · The Journal of Immunology · 1981 · 1.3K citations · Full text