© The Rockefeller University Press, 0022-1007/2000/3/915/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 6, March 20, 2000 915-926
Activation-induced Inhibition of Interleukin 6–mediated T Cell Survival and Signal Transducer and Activator of Transcription 1 Signaling
T. Kent Teaguea,
Brian C. Schaeferb,
David Hildemanb,
Jeremy Bendera,
Tom Mitchella,
John W. Kapplerb,d,e,f, and
Philippa Marrackb,c,d,f
a Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206
b Howard Hughes Medical Institute, National Jewish Medical and Research Center, Denver, Colorado 80206
c Department of Biochemistry and Molecular Biology, University of Colorado Health Sciences Center, Denver, Colorado 80206
d Department of Immunology, University of Colorado Health Sciences Center, Denver, Colorado 80206
e Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80206
f Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80206
Correspondence to:
Philippa Marrack, Howard Hughes Medical Institute, Department of Medicine, 5th Floor Goodman Bldg., National Jewish Medical and Research Center, 1400 Jackson St., Denver, CO 80206. Tel:303-398-1322 Fax:303-398-1396 E-mail:pmarrack{at}njc.org.
Released online: 13 March 2000
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.
Key Words:
cytokine, survival, memory, death, signal transducer and activator of transcription 3
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