Activation-induced inhibition of interleukin 6-mediated T cell survival and signal transducer and activator of transcription 1 signaling.
The cytokines interleukin (IL)-2, IL-4, IL-6, IL-7, and IL-15 have all previously been shown to inhibit resting T cell death in vitro. We have found a difference in the response of T cells to IL-6, depending on the activation status of the cells. IL-6 inhibited the death of naive T cells, but had no effect on the death of either superantigen-activated T cells, or T cells bearing memory markers. This was true even when the resting and activated T cells were isolated from the same animal; thus, the determining factor for IL-6 insensitivity was the activation status or activation history of the cell, and not the milieu in the animal from which the cells were isolated. Activated T cells expressed lower levels of IL-6 receptors on their surfaces, yet there were sufficient levels of receptors for signaling, as we observed similar levels of signal transducer and activator of transcription (Stat)3 phosphorylation in resting and activated T cells treated with IL-6. However, there was profound inhibition of IL-6-induced Stat1 phosphorylation in activated T cells compared with resting T cells. These data suggest that there is activation-induced inhibition of IL-6 receptor signaling in T cells. This inhibition appears to be specific for some but not all of the IL-6-mediated signaling cascades in these cells.
Teague
T K
TK
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Schaefer
B C
BC
Hildeman
D
D
Bender
J
J
Mitchell
T
T
Kappler
J W
JW
Marrack
P
P
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D016923:Cell Death / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D007156:Immunologic Memory; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000502:physiology*; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D000093242:Interleukin-6 Inhibitors
D002352:Carrier Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D000093242:Interleukin-6 Inhibitors; C491590:Socs1 protein, mouse; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse