The role of Fas ligand in immune privilege.
ABSTRACT Immune privilege is a property of some sites in the body, whereby immune responses are limited or prevented. One explanation that has been proposed for this phenomenon is engagement of the pro-apoptotic molecule Fas by its ligand (FasL), which leads to apoptosis, and consequently limits an inflammatory response. This idea has recently been challenged, and here we review the evidence for and against a role for FasL in immune privilege.
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ABSTRACT: Objective. This study investigated the association of the single nucleotide polymorphisms (SNPs) in the FAS and FASL genes with the outcome of hepatitis B virus (HBV) infection. Methods. Blood samples were collected from 116 HBV-infected patients at the Hospital of the Santa Casa de Misericordia Foundation (Belém, PA, Brazil). Seronegative individuals were used as controls. DNA samples were extracted from the leukocytes and assayed using the polymerase chain reaction (PCR) followed by RFLP analysis with restriction endonucleases. Results. The frequencies of the mutant genotypes for -670FAS (GG), Ivs2nt-124FASL (GG), Ivs3nt-169FASL (ΔT/ΔT), and -844FASL (TT) were higher in the HBV patients, and the FAS-1377AA genotype was more frequent in the control group; however, the differences between the allele and genotype frequencies were not statistically significant. When the HBV patient population was divided into two groups (inactive carriers and active chronic hepatitis patients), the mutant genotypes were found to be more prevalent in the active chronic hepatitis group with respect to the FAS gene polymorphisms; however, this difference was not statistically significant. Conclusions. The results suggest that the polymorphisms in FAS and FASL genes are not associated with HBV infection or even with the natural history of the infection in the Brazilian Amazon region.Disease markers 11/2013; 35(6):741-746. DOI:10.1155/2013/964145 · 2.17 Impact Factor
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ABSTRACT: Methamphetamine administration can cause neuronal apoptotic death in the rat brain via activation of the extrinsic cell death pathway (Fas ligand/Fas/caspase-8 cascade). In the present study, we injected mice with a toxic regimen of methamphetamine (10mg/kg×4 given at 2-h intervals) to assess the role of the Fas ligand/Fas/caspase-8 death pathway in their brain. Methamphetamine did cause the appearance of TUNEL-positive cells in the frontal cortex, striatum, and hippocampus of these animals. The number of TUNEL-positive cells was higher in the striatum than in the frontal cortex and hippocampus. Immunohistochemical and immunoblot techniques revealed significant methamphetamine-induced increases in Fas ligand expression and diffuse appearance of the active caspase-8 in these brain regions. Taken together, our data suggest that methamphetamine can cause marked activation of the caspase-8-dependent death pathway in the brain.
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ABSTRACT: The importance of CD4 T cells in orchestrating the immune system and their role in inducing effective T cell-mediated therapies for the treatment of patients with select established malignancies are undisputable. Through a complex and balanced array of direct and indirect mechanisms of cellular activation and regulation, this functionally diverse family of lymphocytes can potentially promote tumor eradication, long-term tumor immunity, and aid in establishing and/or rebalancing immune cell homeostasis through interaction with other immune cell populations within the highly dynamic tumor environment. However, recent studies have uncovered additional functions and roles for CD4 T cells, some of which are independent of other lymphocytes, that can not only influence and contribute to tumor immunity but paradoxically promote tumor growth and progression. Here, we review the recent advances in our understanding of the various CD4 T cell lineages and their signature cytokines in disease progression and/or regression. We discuss their direct and indirect mechanistic interplay among themselves and with other responding cells of the antitumor response, their potential roles and abilities for "plasticity" and memory cell generation within the hostile tumor environment, and their potentials in cancer treatment and immunotherapy.Frontiers in Oncology 03/2013; 3:63. DOI:10.3389/fonc.2013.00063