نتایج جستجو برای: perforin gene
تعداد نتایج: 1142550 فیلتر نتایج به سال:
Intrathymic positive selection matches CD4-CD8 lineage differentiation to MHC specificity. However, it is unclear whether MHC signals induce lineage choice or simply select thymocytes of the appropriate lineage. To investigate this issue, we assessed thymocytes undergoing positive selection for expression of the CD8 lineage markers perforin and Runx3. Using both population-based and single-cell...
Evolution from a furan-containing high-throughput screen (HTS) hit (1) resulted in isobenzofuran-1(3H)-one (2) as a potent inhibitor of the function of both isolated perforin protein and perforin delivered in situ by intact KHYG-1 NK cells. In the current study, structure-activity relationship (SAR) development towards a novel series of diarylthiophene analogues has continued through the use of...
Following its secretion from cytotoxic lymphocytes into the immune synapse, perforin binds to target cell membranes through its Ca(2+)-dependent C2 domain. Membrane-bound perforin then forms pores that allow passage of pro-apoptopic granzymes into the target cell. In the present study, structural and biochemical studies reveal that Ca(2+) binding triggers a conformational change in the C2 domai...
Cytotoxic lymphocytes, NK cells and CD8(+) T cells play a pivotal role in the host defense. To reveal the biological function of these cells through establishing a comprehensive gene expression profile, serial analysis of gene expression was performed in human peripheral blood NK cells and CD8(+) T cells. In total, 85,848 tags corresponding to >20,000 different transcripts were sequenced. The g...
NK1.1+ T (NKT) cells are efficient regulators of early host responses which have been shown to play a role in tumor surveillance. The relevance of NKT cells in immune surveillance of viral infections, however, is not well understood. In this study, we investigated the functional relevance of NKT cells in controlling herpesvirus infections by using challenge with murine cytomegalovirus (MCMV) as...
The pore-forming protein perforin is critical for defense against many human pathogens and for preventing a catastrophic collapse of immune homeostasis, manifested in infancy as Type 2 familial hemophagocytic lymphohistiocytosis (FHL). However, no evidence has yet linked defective perforin cytotoxicity with cancer susceptibility in humans. Here, we examined perforin function in every patient re...
LAMP1/CD107a is required for efficient perforin delivery to lytic granules and NK-cell cytotoxicity.
Secretory lysosomes of natural killer (NK) cells, containing perforin and granzymes, are indispensable for NK-cell cytotoxicity because their release results in the induction of target-cell apoptosis. Lysosome-associated membrane protein (LAMP) 1/CD107a is used as a marker for NK-cell degranulation, but its role in NK-cell biology is unknown. We show that LAMP1 silencing causes inhibition of NK...
BACKGROUND There is mounting evidence that perforin and granzymes are important mediators in the lung destruction seen in COPD. We investigated the characteristics of the three main perforin and granzyme containing peripheral cells, namely CD8+ T lymphocytes, natural killer (NK; CD56+CD3-) cells and NKT-like (CD56+CD3+) cells. METHODS Peripheral blood mononuclear cells (PBMCs) were isolated a...
Stimulation of CD1d-restricted semiinvariant natural killer T cells by using the CD1d ligand alpha-galactosylceramide (alphaGalCer) induces pregnancy loss in mice through an ill-defined mechanism involving TNF, IFN-gamma, and perforin. In this article, we demonstrate that during early gestation, alphaGalCer efficiently induced pregnancy loss in C57BL/6J and BALB/cJ mice in a perforin-dependent ...
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