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 prev iously 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 b earing 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 c ell, and not the milieu in the animal from which the cells were isolated. A ctivated T cells expressed lower levels of IL-6 receptors on their surfaces , yet there were sufficient levels of receptors for signaling, as we observ ed similar levels of signal transducer and activator of transcription (Stat )3 phosphorylation in resting and activated T cells treated with IL-6. Howe ver, there was profound inhibition of IL-6-induced Stat1 phosphorylation in activated T cells compared with resting T cells. These data suggest that t here 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-m ediated signaling cascades in these cells.