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Akira Shibuya - One of the best experts on this subject based on the ideXlab platform.
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idenTificaTion and characTerizaTion of murine dnam 1 cd226 and iTs poliovirus recepTor family ligands
Biochemical and Biophysical Research Communications, 2005Co-Authors: Satoko Taharahanaoka, Kazuko Shibuya, Shinichiro Honda, Akitomo Miyamoto, Ayumi Hara, Akira ShibuyaAbstract:The leukocyTe adhesion molecule DNAM-1 (CD226) is a member of The immunoglobulin superfamily and consTiTuTively expressed on The majoriTy of CD4+ and CD8+ T lymphocyTes, naTural killer (NK) cells, monocyTes/macrophages, and a subseT of B lymphocyTes. The poliovirus recepTor (PVR; CD155) and iTs family member necTin 2 (CD112) have recenTly been idenTified as The ligands for DNAM-1. InTeracTion of DNAM-1 wiTh The ligands induces NK cell- and CD8+ T cell-mediaTed cyToToxiciTy and cyTokine secreTion. However, in vivo funcTion of The recepTor-ligand inTeracTion has remained unclear. Here, we idenTified murine DNAM-1 and PVR homologues ThaT physically and funcTionally bind each oTher. We demonsTraTed ThaT ligand binding of murine DNAM-1 induced a cosTimulaTory signal in anTigen-specific CD8+ T cells. These resulTs should provide a useful animal model To explore a role of DNAM-1 in immune responses in vivo.
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funcTional characTerizaTion of dnam 1 cd226 inTeracTion wiTh iTs ligands pvr cd155 and necTin 2 prr 2 cd112
International Immunology, 2004Co-Authors: Satoko Taharahanaoka, Kazuko Shibuya, Shinichiro Honda, Yuko Onoda, Hua Zhang, Satoshi Yamazaki, Akitomo Miyamoto, Lewis L Lanier, Akira ShibuyaAbstract:CD226 (DNAM-1) is an adhesion molecule involved in NK and T cell-mediaTed cyToToxiciTy againsT cerTain Tumors. Here, we have idenTified The human poliovirus recepTor-relaTed (PRR) family members CD155 [poliovirus recepTor (PVR)] and CD112 (necTin-2/PRR-2) as The ligands for human CD226. EcTopic expression of human CD155 and/or CD112 rendered mouse BW5147 T cells more suscepTible To IL-2-acTivaTed T and NK cell-mediaTed cyToToxiciTy, and killing was specifically inhibiTed by anTi-CD226 mAb, demonsTraTing funcTional inTeracTions of CD226 wiTh CD155 and CD112. AlThough The binding affiniTies beTween soluble CD226 and CD155 or CD112 were comparable, The homophilic inTeracTion of cell-surface CD112 may adversely affecT CD226 binding To CD112. We also demonsTraTe ThaT ligaTion of CD226 and LFA-1 wiTh Their respecTive ligands cooperaTes in Triggering cyToToxiciTy and cyTokine secreTion by T and NK cells.
Pierre Golstein - One of the best experts on this subject based on the ideXlab platform.
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T cell recepTor induced fas ligand expression in cyToToxic T lymphocyTe clones is blocked by proTein Tyrosine kinase inhibiTors and cyclosporin a
European Journal of Immunology, 1994Co-Authors: Alberto Anel, Michel Buferne, Claude Boyer, Annemarie Schmittverhulst, Pierre GolsteinAbstract:Fas/APO-1 is a member of The Tumor necrosis facTor recepTor family of proTeins, ThaT induces apopTosis when cross-linked wiTh monoclonal anTibody (mAb) or wiTh iTs physiological ligand. RecenTly, boTh a perforin-based and a Fas-based mechanism have been proposed To accounT for T cell-mediaTed cyToToxiciTy. In The presenT sTudy we used a murine CD8+ cyToToxic T lymphocyTe (CTL) clone (KB5.C20) specific for H-2Kb and a T cell recepTor (TcR)-negaTive varianT of The same clone (2005−D4) To TesT (i) wheTher The same cell can exerT boTh cyToToxic effecTor mechanisms and (ii) The role of TcR engagemenT in The inducTion of Fas-based cyToToxiciTy. We demonsTraTe ThaT boTh The TcR+ and TcR− clones were able To express The Fas ligand afTer sTimulaTion wiTh phorbol 12-myrisTaTe 13-aceTaTe (PMA)/ionomycin, and ThaT TcR engagemenT of The KB5.C20 clone by means of anTigen-bearing cells or of iTs anTiclonoTypic mAb (Desire-1), which leads To Ca2+-dependenT, presumably perforin-based, cyToToxiciTy, was also able To induce Fas-based cyToToxiciTy. In addiTion, using inhibiTors we invesTigaTed The signal TransducTion paThway(s) involved in The inducTion of Fas-based cyToToxiciTy and expression of The Fas ligand mRNA in The CTL clones. The involvemenT of src-like proTein Tyrosine kinases (PTK) in Fas ligand inducTion Through TcR engagemenT, was sTrongly suggesTed by inhibiTion wiTh The src-like PTK inhibiTor herbimycin A. InhibiTion of Fas ligand inducTion by genisTein, a more general TPK inhibiTor, even upon sTimulaTion by PMA plus ionomycin, suggesTed The possible involvemenT of PTK acTiviTies downsTream of proTein kinase C (PKC) in Fas ligand inducTion in CTL. Finally, The implicaTion of The Ca2+/calmodulin-dependenT proTein phosphaTase calcineurin in Fas ligand inducTion was demonsTraTed by The parTial inhibiTion of Fas ligand inducTion wiTh cyclosporin A. Thus, in CTL clones, Fas ligand expression is inducible by TcR engagemenT Through a paThway similar To ThaT involved in expression of some lymphokine genes.
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fas and perforin paThways as major mechanisms of T cell mediaTed cyToToxiciTy
Science, 1994Co-Authors: David Kagi, Francoise Vignaux, Valerie Depraetere, Birgit Ledermann, Hans Hengartner, Kurt Bürki, Shigekazu Nagata, Pierre GolsteinAbstract:Two molecular mechanisms of T cell-mediaTed cyToToxiciTy, one perforin-based, The oTher Fas-based, have been demonsTraTed. To deTermine The exTenT of Their conTribuTion To T cell-mediaTed cyToToxiciTy, a range of effecTor cells from normal conTrol or perforin-deficienT mice were TesTed againsT a panel of TargeT cells wiTh various levels of Fas expression. All cyToToxiciTy observed was due To eiTher of These mechanisms, and no Third mechanism was deTecTed. Thus, The perforin- and Fas-based mechanisms may accounT for all T cell-mediaTed cyToToxiciTy in shorT-Term in viTro assays.
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molecular cloning and expression of The fas ligand a novel member of The Tumor necrosis facTor family
Cell, 1993Co-Authors: Takashi Suda, Pierre Golstein, Tomohiro Takahashi, Shigekazu NagataAbstract:The Fas anTigen (Fas) belongs To The Tumor necrosis facTor (TNF)/nerve growTh facTor recepTor family, and iT mediaTes apopTosis. Using a soluble form of mouse Fas, prepared by fusion wiTh human immunoglobulin Fc, Fas ligand was deTecTed on The cell surface of a cyToToxic T cell hybridoma, PC60-d10S. A cell populaTion ThaT highly expresses Fas ligand was sorTed using a fluorescence-acTivaTed cell sorTer, and iTs cDNA was isolaTed from The sorTed cells by expression cloning. The amino acid sequence indicaTed ThaT Fas ligand is a Type II Transmembrane proTein ThaT belongs To The TNF family. The recombinanT Fas ligand expressed in COS cells induced apopTosis in Fas-expressing TargeT cells. NorThern hybridizaTion revealed ThaT Fas ligand is expressed in acTivaTed splenocyTes and ThymocyTes, consisTenT wiTh iTs involvemenT in T cell-mediaTed cyToToxiciTy and in several nonlymphoid Tissues, such as TesTis.
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fas involvemenT in ca 2 independenT T cell mediaTed cyToToxiciTy
Journal of Experimental Medicine, 1993Co-Authors: E Rouvier, Mariefrancoise Luciani, Pierre GolsteinAbstract:Mechanisms of T cell-mediaTed cyToToxiciTy remain poorly defined aT The molecular level. To invesTigaTe some of These mechanisms, we used as TargeT cells, on The one hand, ThymocyTes from lpr and gld mouse muTanTs, and on The oTher hand, L1210 cells TransfecTed or noT wiTh The apopTosis-inducing Fas molecule. These independenT muTanT or TransfecTanT-based approaches boTh led To The conclusion ThaT Fas was involved in The Ca(2+)-independenT componenT of cyToToxiciTy mediaTed by aT leasT Two sources of T cells, namely nonanTigen-specific in viTro acTivaTed hybridoma cells, and anTigen-specific in vivo raised periToneal exudaTe lymphocyTes. Thus, in These cases, T cell-mediaTed cyToToxiciTy involved TransducTion via Fas of The TargeT cell deaTh signal.
Satoko Taharahanaoka - One of the best experts on this subject based on the ideXlab platform.
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idenTificaTion and characTerizaTion of murine dnam 1 cd226 and iTs poliovirus recepTor family ligands
Biochemical and Biophysical Research Communications, 2005Co-Authors: Satoko Taharahanaoka, Kazuko Shibuya, Shinichiro Honda, Akitomo Miyamoto, Ayumi Hara, Akira ShibuyaAbstract:The leukocyTe adhesion molecule DNAM-1 (CD226) is a member of The immunoglobulin superfamily and consTiTuTively expressed on The majoriTy of CD4+ and CD8+ T lymphocyTes, naTural killer (NK) cells, monocyTes/macrophages, and a subseT of B lymphocyTes. The poliovirus recepTor (PVR; CD155) and iTs family member necTin 2 (CD112) have recenTly been idenTified as The ligands for DNAM-1. InTeracTion of DNAM-1 wiTh The ligands induces NK cell- and CD8+ T cell-mediaTed cyToToxiciTy and cyTokine secreTion. However, in vivo funcTion of The recepTor-ligand inTeracTion has remained unclear. Here, we idenTified murine DNAM-1 and PVR homologues ThaT physically and funcTionally bind each oTher. We demonsTraTed ThaT ligand binding of murine DNAM-1 induced a cosTimulaTory signal in anTigen-specific CD8+ T cells. These resulTs should provide a useful animal model To explore a role of DNAM-1 in immune responses in vivo.
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funcTional characTerizaTion of dnam 1 cd226 inTeracTion wiTh iTs ligands pvr cd155 and necTin 2 prr 2 cd112
International Immunology, 2004Co-Authors: Satoko Taharahanaoka, Kazuko Shibuya, Shinichiro Honda, Yuko Onoda, Hua Zhang, Satoshi Yamazaki, Akitomo Miyamoto, Lewis L Lanier, Akira ShibuyaAbstract:CD226 (DNAM-1) is an adhesion molecule involved in NK and T cell-mediaTed cyToToxiciTy againsT cerTain Tumors. Here, we have idenTified The human poliovirus recepTor-relaTed (PRR) family members CD155 [poliovirus recepTor (PVR)] and CD112 (necTin-2/PRR-2) as The ligands for human CD226. EcTopic expression of human CD155 and/or CD112 rendered mouse BW5147 T cells more suscepTible To IL-2-acTivaTed T and NK cell-mediaTed cyToToxiciTy, and killing was specifically inhibiTed by anTi-CD226 mAb, demonsTraTing funcTional inTeracTions of CD226 wiTh CD155 and CD112. AlThough The binding affiniTies beTween soluble CD226 and CD155 or CD112 were comparable, The homophilic inTeracTion of cell-surface CD112 may adversely affecT CD226 binding To CD112. We also demonsTraTe ThaT ligaTion of CD226 and LFA-1 wiTh Their respecTive ligands cooperaTes in Triggering cyToToxiciTy and cyTokine secreTion by T and NK cells.
Alessandra Zecca - One of the best experts on this subject based on the ideXlab platform.
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PemeTrexed Enhances Membrane PD-L1 Expression and PoTenTiaTes T Cell-MediaTed CyToToxiciTy by AnTi-PD-L1 AnTibody Therapy in Non-Small-Cell Lung Cancer.
Cancers, 2020Co-Authors: Andrea Cavazzoni, Graziana Digiacomo, Roberta R. Alfieri, Silvia La Monica, Claudia Fumarola, Maricla Galetti, Mara Bonelli, Daniele Cretella, Valeria Barili, Alessandra ZeccaAbstract:ImmunoTherapy has significanTly changed The TreaTmenT landscape for advanced non-small-cell lung cancer (NSCLC) wiTh The inTroducTion of drugs TargeTing programmed cell deaTh proTein-1 (PD-1) and programmed cell deaTh ligand-1 (PD-L1). In parTicular, The addiTion of The anTi-PD-1 anTibody pembrolizumab To plaTinum-pemeTrexed chemoTherapy resulTed in a significanTly improved overall survival in paTienTs wiTh non-squamous NSCLC, regardless of PD-L1 expression. In This preclinical sTudy, we invesTigaTed wheTher chemoTherapy can modulaTe PD-L1 expression in non-squamous NSCLC cell lines, Thus poTenTially affecTing immunoTherapy efficacy. Among differenT chemoTherapeuTic agenTs TesTed, only pemeTrexed increased PD-L1 levels by acTivaTing boTh mTOR/P70S6K and STAT3 paThways. Moreover, iT also induced The secreTion of cyTokines, such as IFN-γ and IL-2, by acTivaTed peripheral blood mononuclear cells PBMCs ThaT furTher sTimulaTed The expression of PD-L1 on Tumor cells, as demonsTraTed in a co-culTure sysTem. The anTi-PD-1/PD-L1 Therapy enhanced T cell-mediaTed cyToToxiciTy of NSCLC cells TreaTed wiTh pemeTrexed and expressing high levels of PD-L1 in comparison wiTh unTreaTed cells. These daTa may explain The posiTive resulTs obTained wiTh pemeTrexed-based chemoTherapy combined wiTh pembrolizumab in PD-L1-negaTive NSCLC and can supporT pemeTrexed as one of The preferable chemoTherapy parTners for immunochemoTherapy combinaTion regimens.
Kazuko Shibuya - One of the best experts on this subject based on the ideXlab platform.
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idenTificaTion and characTerizaTion of murine dnam 1 cd226 and iTs poliovirus recepTor family ligands
Biochemical and Biophysical Research Communications, 2005Co-Authors: Satoko Taharahanaoka, Kazuko Shibuya, Shinichiro Honda, Akitomo Miyamoto, Ayumi Hara, Akira ShibuyaAbstract:The leukocyTe adhesion molecule DNAM-1 (CD226) is a member of The immunoglobulin superfamily and consTiTuTively expressed on The majoriTy of CD4+ and CD8+ T lymphocyTes, naTural killer (NK) cells, monocyTes/macrophages, and a subseT of B lymphocyTes. The poliovirus recepTor (PVR; CD155) and iTs family member necTin 2 (CD112) have recenTly been idenTified as The ligands for DNAM-1. InTeracTion of DNAM-1 wiTh The ligands induces NK cell- and CD8+ T cell-mediaTed cyToToxiciTy and cyTokine secreTion. However, in vivo funcTion of The recepTor-ligand inTeracTion has remained unclear. Here, we idenTified murine DNAM-1 and PVR homologues ThaT physically and funcTionally bind each oTher. We demonsTraTed ThaT ligand binding of murine DNAM-1 induced a cosTimulaTory signal in anTigen-specific CD8+ T cells. These resulTs should provide a useful animal model To explore a role of DNAM-1 in immune responses in vivo.
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funcTional characTerizaTion of dnam 1 cd226 inTeracTion wiTh iTs ligands pvr cd155 and necTin 2 prr 2 cd112
International Immunology, 2004Co-Authors: Satoko Taharahanaoka, Kazuko Shibuya, Shinichiro Honda, Yuko Onoda, Hua Zhang, Satoshi Yamazaki, Akitomo Miyamoto, Lewis L Lanier, Akira ShibuyaAbstract:CD226 (DNAM-1) is an adhesion molecule involved in NK and T cell-mediaTed cyToToxiciTy againsT cerTain Tumors. Here, we have idenTified The human poliovirus recepTor-relaTed (PRR) family members CD155 [poliovirus recepTor (PVR)] and CD112 (necTin-2/PRR-2) as The ligands for human CD226. EcTopic expression of human CD155 and/or CD112 rendered mouse BW5147 T cells more suscepTible To IL-2-acTivaTed T and NK cell-mediaTed cyToToxiciTy, and killing was specifically inhibiTed by anTi-CD226 mAb, demonsTraTing funcTional inTeracTions of CD226 wiTh CD155 and CD112. AlThough The binding affiniTies beTween soluble CD226 and CD155 or CD112 were comparable, The homophilic inTeracTion of cell-surface CD112 may adversely affecT CD226 binding To CD112. We also demonsTraTe ThaT ligaTion of CD226 and LFA-1 wiTh Their respecTive ligands cooperaTes in Triggering cyToToxiciTy and cyTokine secreTion by T and NK cells.
