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Thomas Spies - One of the best experts on this subject based on the ideXlab platform.
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fas ligand mediaTed paracrine T Cell regulaTion by The recepTor nkg2d in Tumor immuniTy
Nature Immunology, 2006Co-Authors: Veronika Groh, Kimberly S. Smythe, Zhengpeng Dai, Thomas SpiesAbstract:Tumor-associaTed ligands of The acTivaTing NKG2D recepTor can effecTively sTimulaTe T Cell responses aT early buT noT laTe sTages of Tumor growTh. In laTe-sTage human Tumor seTTings, we observed MIC-driven proliferaTion of NKG2D(+)CD4(+) T Cells ThaT produced The cyTokine Fas ligand (FasL) as a resulT of NKG2D cosTimulaTion buT were Themselves proTecTed from Fas-mediaTed growTh arresT. In conTrasT, FasL suppressed proliferaTion of T Cells in viTro ThaT did noT receive NKG2D cosTimulaTion. Similar observaTions wiTh normal peripheral blood NKG2D(+)CD8(+) T Cells demonsTraTed unrecognized NKG2D-mediaTed immune funcTions, whereby FasL release promoTes Tumor Cell deaTh and NKG2D cosTimulaTion prolongs T Cell survival. These effecTs, beneficial in condiTions of limiTed NKG2D ligand expression, may be counTerweighed when massive expression and shedding of MIC occurs, such as in some laTe-sTage Tumors, ThaT causes susTained NKG2D cosTimulaTion and populaTion expansion of immunosuppressive T Cells.
Angus W Thomson - One of the best experts on this subject based on the ideXlab platform.
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rapamycin TreaTed alloanTigen pulsed hosT dendriTic Cells induce ag specific T Cell regulaTion and prolong grafT survival
American Journal of Transplantation, 2005Co-Authors: Timucin Taner, Holger Hackstein, Zhiliang Wang, Adrian E Morelli, Angus W ThomsonAbstract:Tolerogenic properTies of dendriTic Cells (DC), parTicularly Those in The immaTure sTaTe, and Their TherapeuTic poTenTial are increasingly being recognized. Among several disTincT approaches To generaTe sTably immaTure DC, pharmacologic manipulaTion sTands ouT as a promising and clinically applicable opTion. We have shown recenTly ThaT The immunophilin ligand rapamycin (Rapa) can inhibiT DC maTuraTion and Their effecTor funcTions. Here, we examined The impacT of Rapa exposure on subsequenT alloanTigen (Ag) presenTaTion by myeloid DC via The indirecT paThway. Rapa-TreaTed, allogeneic lysaTe-pulsed hosT DC (Rapa-DC) were inferior sTimulaTors of syngeneic T Cells, compared To lysaTe-pulsed conTrol DC. Rapa exposure did noT block alloAg upTake by DC nor impair Their in vivo homing To splenic T Cell areas afTer adopTive Transfer. T Cells primed by Rapa-TreaTed, alloAg-pulsed DC showed decreased capaciTy To produce IL-2 and IFNγ, and were hyporesponsive To subsequenT challenge via boTh The direcT and indirecT paThways, in an Ag-specific manner. When infused 1 week before TransplanTaTion, These Rapa-DC significanTly prolonged alloAg-specific hearT grafT survival. This effecT was reversed by sysTemic IL-2 adminisTraTion buT enhanced by eiTher repeaTed infusion of The Cells or a shorT posT-TransplanT course of FK506. These TherapeuTic effecTs, achieved by TargeTing boTh major paThways of allorecogniTion, provide The basis for a clinically applicable sTraTegy To suppress grafT rejecTion.
Veronika Groh - One of the best experts on this subject based on the ideXlab platform.
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fas ligand mediaTed paracrine T Cell regulaTion by The recepTor nkg2d in Tumor immuniTy
Nature Immunology, 2006Co-Authors: Veronika Groh, Kimberly S. Smythe, Zhengpeng Dai, Thomas SpiesAbstract:Tumor-associaTed ligands of The acTivaTing NKG2D recepTor can effecTively sTimulaTe T Cell responses aT early buT noT laTe sTages of Tumor growTh. In laTe-sTage human Tumor seTTings, we observed MIC-driven proliferaTion of NKG2D(+)CD4(+) T Cells ThaT produced The cyTokine Fas ligand (FasL) as a resulT of NKG2D cosTimulaTion buT were Themselves proTecTed from Fas-mediaTed growTh arresT. In conTrasT, FasL suppressed proliferaTion of T Cells in viTro ThaT did noT receive NKG2D cosTimulaTion. Similar observaTions wiTh normal peripheral blood NKG2D(+)CD8(+) T Cells demonsTraTed unrecognized NKG2D-mediaTed immune funcTions, whereby FasL release promoTes Tumor Cell deaTh and NKG2D cosTimulaTion prolongs T Cell survival. These effecTs, beneficial in condiTions of limiTed NKG2D ligand expression, may be counTerweighed when massive expression and shedding of MIC occurs, such as in some laTe-sTage Tumors, ThaT causes susTained NKG2D cosTimulaTion and populaTion expansion of immunosuppressive T Cells.
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Corrigendum: Fas ligand–mediaTed paracrine T Cell regulaTion by The recepTor NKG2D in Tumor immuniTy
Nature Immunology, 2006Co-Authors: Veronika Groh, Kimberly S. Smythe, Zhengpeng Dai, Thomas A. SpiesAbstract:Corrigendum: Fas ligand–mediaTed paracrine T Cell regulaTion by The recepTor NKG2D in Tumor immuniTy
Timucin Taner - One of the best experts on this subject based on the ideXlab platform.
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rapamycin TreaTed alloanTigen pulsed hosT dendriTic Cells induce ag specific T Cell regulaTion and prolong grafT survival
American Journal of Transplantation, 2005Co-Authors: Timucin Taner, Holger Hackstein, Zhiliang Wang, Adrian E Morelli, Angus W ThomsonAbstract:Tolerogenic properTies of dendriTic Cells (DC), parTicularly Those in The immaTure sTaTe, and Their TherapeuTic poTenTial are increasingly being recognized. Among several disTincT approaches To generaTe sTably immaTure DC, pharmacologic manipulaTion sTands ouT as a promising and clinically applicable opTion. We have shown recenTly ThaT The immunophilin ligand rapamycin (Rapa) can inhibiT DC maTuraTion and Their effecTor funcTions. Here, we examined The impacT of Rapa exposure on subsequenT alloanTigen (Ag) presenTaTion by myeloid DC via The indirecT paThway. Rapa-TreaTed, allogeneic lysaTe-pulsed hosT DC (Rapa-DC) were inferior sTimulaTors of syngeneic T Cells, compared To lysaTe-pulsed conTrol DC. Rapa exposure did noT block alloAg upTake by DC nor impair Their in vivo homing To splenic T Cell areas afTer adopTive Transfer. T Cells primed by Rapa-TreaTed, alloAg-pulsed DC showed decreased capaciTy To produce IL-2 and IFNγ, and were hyporesponsive To subsequenT challenge via boTh The direcT and indirecT paThways, in an Ag-specific manner. When infused 1 week before TransplanTaTion, These Rapa-DC significanTly prolonged alloAg-specific hearT grafT survival. This effecT was reversed by sysTemic IL-2 adminisTraTion buT enhanced by eiTher repeaTed infusion of The Cells or a shorT posT-TransplanT course of FK506. These TherapeuTic effecTs, achieved by TargeTing boTh major paThways of allorecogniTion, provide The basis for a clinically applicable sTraTegy To suppress grafT rejecTion.
Kimberly S. Smythe - One of the best experts on this subject based on the ideXlab platform.
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fas ligand mediaTed paracrine T Cell regulaTion by The recepTor nkg2d in Tumor immuniTy
Nature Immunology, 2006Co-Authors: Veronika Groh, Kimberly S. Smythe, Zhengpeng Dai, Thomas SpiesAbstract:Tumor-associaTed ligands of The acTivaTing NKG2D recepTor can effecTively sTimulaTe T Cell responses aT early buT noT laTe sTages of Tumor growTh. In laTe-sTage human Tumor seTTings, we observed MIC-driven proliferaTion of NKG2D(+)CD4(+) T Cells ThaT produced The cyTokine Fas ligand (FasL) as a resulT of NKG2D cosTimulaTion buT were Themselves proTecTed from Fas-mediaTed growTh arresT. In conTrasT, FasL suppressed proliferaTion of T Cells in viTro ThaT did noT receive NKG2D cosTimulaTion. Similar observaTions wiTh normal peripheral blood NKG2D(+)CD8(+) T Cells demonsTraTed unrecognized NKG2D-mediaTed immune funcTions, whereby FasL release promoTes Tumor Cell deaTh and NKG2D cosTimulaTion prolongs T Cell survival. These effecTs, beneficial in condiTions of limiTed NKG2D ligand expression, may be counTerweighed when massive expression and shedding of MIC occurs, such as in some laTe-sTage Tumors, ThaT causes susTained NKG2D cosTimulaTion and populaTion expansion of immunosuppressive T Cells.
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Corrigendum: Fas ligand–mediaTed paracrine T Cell regulaTion by The recepTor NKG2D in Tumor immuniTy
Nature Immunology, 2006Co-Authors: Veronika Groh, Kimberly S. Smythe, Zhengpeng Dai, Thomas A. SpiesAbstract:Corrigendum: Fas ligand–mediaTed paracrine T Cell regulaTion by The recepTor NKG2D in Tumor immuniTy
