Regulation of TRAIL Expression in T helper cells (85.17)

Abstract

Abstract TNF-related apoptosis-inducing ligand (TRAIL/Apo2 ligand), along with FasL and TNFα, is one of three members of the TNF cytokine family that induce apoptosis. TRAIL can bind to several different receptors including those containing a cytoplasmic death domain and others that lack such a domain, termed decoy receptors. Here we found that TRAIL was preferentially expressed in Th2 cells, and, though exogenous TRAIL did not cause death in these cells, it did induce apoptosis of Th1 cells. Since it differentially induced apoptosis in Th1 and Th2 cells, TRAIL was likely to modulate the balance between them in determining the type of immune response. However, the regulation mechanism of TRAIL expression in T lymphocytes is not fully understood. We showed that A1.1 T hybridoma cells constitutively expressed TRAIL at a low level that could be boosted by adding IFN-γ. When Th2 cells were treated with high dosage of IFN-γ upon restimulation, TRAIL expression was boosted as well, whereas when Th1 cells were treated with high dosage of IL-4 upon restimulation, TRAIL was surprisingly detected at a comparable level to that in Th2 cells without any cytokine treatment. Interestingly, although Th1 cells were the main producers of IFNγ, Th2 cells expressed IFNγ receptors. All these results suggest that IFN-γ secreted by Th1 cells and IL-4 secreted by Th2 cells may be potent inducers of TRAIL under certain circumstances and therefore can provide some insight into clinical applications.