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.
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20 March 2000
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March 13 2000
Activation-Induced Inhibition of Interleukin 6–Mediated T Cell Survival and Signal Transducer and Activator of Transcription 1 Signaling
T. Kent Teague,
T. Kent Teague
aDepartment of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206
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Brian C. Schaefer,
Brian C. Schaefer
bHoward Hughes Medical Institute, National Jewish Medical and Research Center, Denver, Colorado 80206
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David Hildeman,
David Hildeman
bHoward Hughes Medical Institute, National Jewish Medical and Research Center, Denver, Colorado 80206
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Jeremy Bender,
Jeremy Bender
aDepartment of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206
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Tom Mitchell,
Tom Mitchell
aDepartment of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206
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John W. Kappler,
John W. Kappler
bHoward Hughes Medical Institute, National Jewish Medical and Research Center, Denver, Colorado 80206
dDepartment of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80206
eDepartment of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80206
fDepartment of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80206
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Philippa Marrack
Philippa Marrack
bHoward Hughes Medical Institute, National Jewish Medical and Research Center, Denver, Colorado 80206
cDepartment of Biochemistry and Molecular Biology, University of Colorado Health Sciences Center, Denver, Colorado 80206
dDepartment of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80206
fDepartment of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80206
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T. Kent Teague
aDepartment of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206
Brian C. Schaefer
bHoward Hughes Medical Institute, National Jewish Medical and Research Center, Denver, Colorado 80206
David Hildeman
bHoward Hughes Medical Institute, National Jewish Medical and Research Center, Denver, Colorado 80206
Jeremy Bender
aDepartment of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206
Tom Mitchell
aDepartment of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206
John W. Kappler
bHoward Hughes Medical Institute, National Jewish Medical and Research Center, Denver, Colorado 80206
dDepartment of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80206
eDepartment of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80206
fDepartment of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80206
Philippa Marrack
bHoward Hughes Medical Institute, National Jewish Medical and Research Center, Denver, Colorado 80206
cDepartment of Biochemistry and Molecular Biology, University of Colorado Health Sciences Center, Denver, Colorado 80206
dDepartment of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80206
fDepartment of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80206
Abbreviations used in this paper: HPRT, hypoxanthine ribosyltransferase; Jak, Janus kinase; PI, propidium iodide; PIAS, protein inhibitor of activated Stat; SEA and SEB, staphylococcal enterotoxin A and B; SOCS, suppressor of cytokine signaling; Stat, signal transducer and activator of transcription.
Received:
October 21 1999
Revision Requested:
December 28 1999
Accepted:
January 07 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 191 (6): 915–926.
Article history
Received:
October 21 1999
Revision Requested:
December 28 1999
Accepted:
January 07 2000
Citation
T. Kent Teague, Brian C. Schaefer, David Hildeman, Jeremy Bender, Tom Mitchell, John W. Kappler, Philippa Marrack; Activation-Induced Inhibition of Interleukin 6–Mediated T Cell Survival and Signal Transducer and Activator of Transcription 1 Signaling. J Exp Med 20 March 2000; 191 (6): 915–926. doi: https://doi.org/10.1084/jem.191.6.915
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