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Abstract: Th1 cells are remarkably more susceptible to activation induced cell death than Th17. Here, we compared cultures of these two cell subpopulations for their expression of apoptosis-related molecules when re-exposed to their specific antigen. We also compared the expression of apoptosis-related molecules in the mouse eye with inflammation induced by Th1 or Th17 cells. Using qPCR we found that the mRNA transcript levels of the majority of tested apoptosis-related molecules were higher in the Th1 cultures, and in eyes with Th1-induced inflammation. Apoptotic intrinsic pathway molecules played minor roles in the processes in vitro or in vivo, whereas extrinsic pathway molecules, as well as PD-1, its ligands and Tim3, were heavily involved. [Copyright &y& Elsevier]

Programmed cell death (PCD) is a key process in the regulation of immune cell development and peripheral immune homeostasis. Caspase-dependent apoptosis, as well as a number of alternative cell death mechanisms, account for immune cell PCD induced by cell-intrinsic and extrinsic pathways. In animal models, compelling evidence has emerged that genetic defects in PCD can result in autoimmune disease. Autoimmune disease can arise from single-gene mutations that affect PCD, and defective PCD has been observed in some tissues and cells from patients with rheumatic disease. Selectively inducing PCD in autoreactive B and T cells is very attractive as a therapeutic strategy because it offers the possibility of permanent elimination of these pathogenic cell subsets. In addition, the anti-inflammatory effects of apoptotic cells may add to the therapeutic benefit of induced PCD. Immune cell subsets vary widely in their sensitivity to specific inducers of cell death, and understanding these differences is key to predicting the outcome of inducing apoptosis for therapeutic means. Here, we review approaches that have been used to induce PCD in the treatment of autoimmune disease, and describe the prospects of bringing these experimental strategies into clinical practice. [ABSTRACT FROM AUTHOR]

Recently, we identified Insulinoma-Glucagonoma clone 20 (IG20) that can render cells more susceptible to tumor necrosis factor-alpha (TNF-a)-induced apoptosis. In addition, it can slow cell proliferation, and enhance drug- and radiation-induced cell death. TNF-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in some cancer cells and render others susceptible to cotreatment with drugs and irradiation, with little or no effect on most normal cells. In this study, we investigated the potential of IG20 to enhance TRAIL-induced apoptosis and found that it can render cells more susceptible to TRAIL treatment through enhanced activation of caspases. Further, we showed that this effect can be suppressed by caspase inhibitors, p35 and CrmA, and a dominant-negative Fas-associated death domain-containing protein (DN-FADD). Results from colocalization and immunoprecipitation studies showed that IG20 can interact with TRAIL death receptors (DR), DR4 and DR5 and increase recruitment of FADD and caspase-8 into the TRAIL death-inducing signaling complex (DISC). These results indicate that IG20 is a novel protein that can enhance TRAIL-induced apoptosis by facilitating DISC formation.Oncogene (2004) 23, 6083-6094. doi:10.1038/sj.onc.1207804 Published online 21 June 2004 [ABSTRACT FROM AUTHOR]