Inhibition of T–Cell Responses by Hepatic Stellate Cells Via B7–H1-Mediated T–Cell Apoptosis in Mice

Tolerogenic maturation of liver sinusoidal endothelial cells promotes B7-homolog 1-dependent CD8+ T cell tolerance

“…40 Additionally, T cell apoptosis induction by hepatocytes and hepatic stellate cells was shown to be B7-H1 dependent. 41,42 The apparent contradictory promotion of CD8 ϩ T cell survival by LSEC-derived B7-H1 signaling could be attributable to lack of costimulatory molecules on LSEC or the additional production of cytokines such as transforming growth factor beta by stellate cells. 42 Hepatocytes induce B7-H1-dependent apoptosis in activated T cells.…”

Targeting the PD1/PD-L1 axis in melanoma: Biological rationale, clinical challenges and opportunities

“…PD-L1-deficient mice do not develop spontaneous autoimmune diseases, mild-to-moderate levels of lymphocyte accumulation are evident in the kidneys, liver, and lung, with a predominant CD3+/CD8+ component exhibiting significantly decreased apoptosis [44]. Although the mechanism underlying selective accumulation of CD8+ T cells in PD-L1−/− mice remains to be clarified, these findings implicate a role for PD-L1 in the maintenance of T and cell homeostasis in peripheral organs.…”

Current insights into the regulation of programmed cell death by NF-κB

“…CYLD has recently been shown to also be important for T-cell development and has been implicated to promote deubiquitination of the T-cell-specific tyrosine kinase Lck (Reiley et al, 2006). NF-kB-induced cell death has also been linked to increased expression of the pro-death factors B7-H1 (PCD ligand 1, pdcd1), which induces apoptosis of T lymphocytes (Dong et al, 2002;Yu et al, 2004;Lee et al, 2005), and caspase-11, which can activate the death effector caspase-3 (Kang et al, 2000;Schauvliege et al, 2002). Additionally, NF-kB can function indirectly to activate genes that regulate cell death via upregulation of other transcription factors like p53 or IRF-1, which acts along with NF-kB to stimulate production of the death-promoting inducible nitric oxide synthase after ischemic injury (Wu and Lozano, 1994;reviewed in Denk et al, 2000).…”