SummaryInterleukin-7 (IL-7) is a crucial cytokine involved in T-cell survival and development but its signalling in human T cells, particularly in effector/ memory T cells, is poorly documented. In this study, we found that IL-7 protects human CD4 + effector/memory T cells from apoptosis induced upon the absence of stimulation and cytokines. We show that IL-7 upregulates not only Bcl-2 but also Bcl-xL and Mcl-1 as well. Interleukin-7-induced activation of the janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is sufficient for cell survival and up-regulation of Bcl-2 proteins. In contrast to previous studies with naive T cells, we found that IL-7 is a weak activator of the phosphatidylinositol 3 kinase (PI3K)/AKT (also referred as protein kinase B) pathway and IL-7-mediated cell survival occurs independently from the PI3K/AKT pathway as well as from activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Considering the contribution of both IL-7 and CD4 + effector/memory T cells to the pathogenesis of autoimmune diseases such as rheumatoid arthritis and colitis, our study suggests that IL-7 can contribute to these diseases by promoting cell survival. A further understanding of the mechanisms of IL-7 signalling in effector/memory T cells associated with autoimmune inflammatory diseases may lead to potential new therapeutic avenues.

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Resistance of malignant melanoma cells to Fas-mediated apoptosis is among the mechanisms by which they escape immune surveillance. However, the mechanisms contributing to their resistance are not completely understood, and it is still unclear whether antiapoptotic Bcl-2 -related family proteins play a role in this resistance. In this study, we report that treatment of Fas-resistant melanoma cell lines with cycloheximide, a general inhibitor of de novo protein synthesis, sensitizes them to anti-Fas monoclonal antibody (mAb) -induced apoptosis. The cycloheximide-induced sensitization to Fas-induced apoptosis is associated with a rapid down-regulation of Mcl-1 protein levels, but not that of Bcl-2 or Bcl-xL. Targeting Mcl-1 in these melanoma cell lines with specific small interfering RNA was sufficient to sensitize them to both anti-Fas mAb-induced apoptosis and activation of caspase-9.