Dendritic Cells and Stat3 Are Essential for CD137-Induced CD8 T Cell Activation-Induced Cell Death

Abstract

Material

4-1BB signaling beyond T cells

“…15 Confirmation that DCs express functional 4-1BB came from Wilcox et al 4 These authors observed that administration of in vivo agonistic anti-4-1BB monoclonal antibody (mAb) to naive mice enhanced the ability of DCs to stimulate in vitro T cell-proliferative responses to both alloantigens and nominal antigens. 4 In addition, Zhang et al 18 underscored the importance of 4-1BB signaling in DCs during viral infection; they showed that in vitro activation of DCs by anti-4-1BB led to phosphorylation of STAT3, which in turn strengthened CD8…”

Intervention with costimulatory pathways as a therapeutic approach for graft-versus-host disease

“…However, there is evidence showing that agonistic anti-CD137 mAb can delete Ag-specific CD8 + T cells as well as CD4 + T cells in vivo (Zhang et al, 2007(Zhang et al, , 2010. Earlier treatment with agonistic anti-CD137 mAb maintains elevated levels of TNF-α in LCMV (lymphocytic choriomeningitis virus)-infected mice, leading to Fas expression on activated CD8 + T cells and this in turn results in Fas-mediated T-cell apoptosis (Zhang et al, 2007).…”

“…Earlier treatment with agonistic anti-CD137 mAb maintains elevated levels of TNF-α in LCMV (lymphocytic choriomeningitis virus)-infected mice, leading to Fas expression on activated CD8 + T cells and this in turn results in Fas-mediated T-cell apoptosis (Zhang et al, 2007). Even though Fas-mediated death signal is not sufficient to delete LCMV antigen-specific CD8 + T cells, STAT3 activation by signaling through CD137 in DCs is required for their complete AICD (Zhang et al, 2010). In the C57BL/6→unirradiated BDF1 aGVHD model, agonistic anti-CD137 mAb can completely delete not only donor CD4 + T cells but also donor CD8 + T cells (our unpublished data).…”

Anti-CD137 mAb Deletes Both Donor CD4+and CD8+T Cells in Acute Graft-versus-host Disease

“…However, there is evidence showing that agonistic anti-CD137 mAb can delete antigen-specific CD8 + T cells as well as CD4 + T cells in vivo (6,7). Earlier treatment with agonistic anti-CD137 mAb maintains elevated levels of TNF-α in lymphocytic choriomeningitis virus (LCMV)-infected mice, leading to Fas expression on activated CD8 + T cells and this in turn results in Fas-mediated apoptosis (6).…”

“…Earlier treatment with agonistic anti-CD137 mAb maintains elevated levels of TNF-α in lymphocytic choriomeningitis virus (LCMV)-infected mice, leading to Fas expression on activated CD8 + T cells and this in turn results in Fas-mediated apoptosis (6). Even though Fas-mediated death signal is not sufficient to delete LCMV antigen-specific CD8 + T cells, STAT3 activation by signaling through CD137 in dendritic cells is required for their complete AICD (7). In this study, we showed that agonistic anti-CD137 mAb could completely delete not only donor CD4 + T cells but also CD8 + T cells in the C57BL/6→BDF1 aGVHD model.…”