Ligand-induced desensitization of interleukin 1 receptor-initiated intracellular signaling events in T helper lymphocytes.
Although interleukin 1 (IL-1) receptor signaling events in T helper lymphocytes are incompletely characterized, events associated with translocation of the transcription factor NF-kappa B are receptor-proximal assays of ligand-initiated responses. In this report we demonstrate that the transient nature of IL-1-induced NF-kappa B nuclear translocation occurs as a consequence of ligand-induced receptor desensitization. Other receptor-initiated events including induction of I kappa B alpha phosphorylation, expression of c-jun and junB mRNA, and costimulatory effects on IL-2 synthesis also are altered by IL-1 receptor desensitization. IL-1 receptor desensitization is not initiated by tumor necrosis factor, which also stimulates NF-kappa B translocation, and is not a consequence of alterations in either IL-1 receptor expression or binding affinity. In the absence of IL-1, the effects of desensitization are completely reversed within 18 h. Since IL-1 desensitization is initiated under conditions of low receptor occupancy, it is likely that receptor desensitization results from alterations to a receptor-proximal transducer, rather than from direct modification of the IL-1 receptor. These results suggest that the cyclic nature of the events in the T helper lymphocyte activation program can be controlled, in part, by the reversible desensitization of cell surface IL-1 receptors.
McKean
D J
DJ
Department of Immunology, Mayo Clinic, Rochester, Minnesota 55905.
Huntoon
C
C
Bell
M
M
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D007375:Interleukin-1 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*
D007375:Interleukin-1; D016328:NF-kappa B; D016755:Proto-Oncogene Proteins c-jun; D017472:Receptors, Interleukin-1