T Cell Development

14,000,000 Leading Edge Experts on the ideXlab platform

Scan Science and Technology

Contact Leading Edge Experts & Companies

Scan Science and Technology

Contact Leading Edge Experts & Companies

The Experts below are selected from a list of 216165 Experts worldwide ranked by ideXlab platform

Remy Bosselut - One of the best experts on this subject based on the ideXlab platform.

  • cbfb myh11 hinders early T Cell developmenT and induces massive Cell deaTh in The Thymus
    Blood, 2007
    Co-Authors: Ling Zhao, Martha Kirby, Lucio H. Castilla, Liping Xu, Jennifer L Cannons, Pamela L Schwartzberg, Stacie M. Anderson, Remy Bosselut
    Abstract:

    RecenT sTudies suggesT ThaT The chromosome 16 inversion, associaTed wiTh acuTe myeloid leukemia M4Eo, Takes place in hemaTopoieTic sTem Cells. If This is The case, iT is of inTeresT To know The effecTs of The resulTing fusion gene, CBFB-MYH11, on oTher lineages. Here we sTudied T-Cell developmenT in mice expressing Cbfb-MYH11 and compared Them wiTh mice compound-heTerozygous for a Cbfb null and a hypomorphic GFP knock-in allele (Cbfb−/GFP), which had severe Cbfb deficiency. We found a differenTiaTion block aT The DN1 sTage of ThymocyTe developmenT in Cbfb-MYH11 knock-in chimeras. In a condiTional knock-in model in which Cbfb-MYH11 expression was acTivaTed by Lck-Cre, There was a 10-fold reducTion in ThymocyTe numbers in adulT Thymus, resulTing mainly from impaired survival of CD4+CD8+ ThymocyTes. AlThough Cbfb-MYH11 derepressed CD4 expression efficienTly in reporTer assays, such derepression was less pronounced in vivo. On The oTher hand, CD4 expression was derepressed and ThymocyTe developmenT was blocked aT DN1 and DN2 sTages in E17.5 Cbfb−/GFP Thymus, wiTh a 20-fold reducTion of ToTal ThymocyTe numbers. Our daTa suggesT ThaT Cbfb-MYH11 suppressed Cbfb in several sTages of T-Cell developmenT and provide a mechanism for CBFB-MYH11 associaTion wiTh myeloid buT noT lymphoid leukemia.

  • cbfb myh11 hinders early T Cell developmenT and induces massive Cell deaTh in The Thymus
    Blood, 2007
    Co-Authors: Ling Zhao, Martha Kirby, Lucio H. Castilla, Liping Xu, Jennifer L Cannons, Pamela L Schwartzberg, Stacie M. Anderson, Remy Bosselut
    Abstract:

    RecenT sTudies suggesT ThaT The chromosome 16 inversion, associaTed wiTh acuTe myeloid leukemia M4Eo, Takes place in hemaTopoieTic sTem Cells. If This is The case, iT is of inTeresT To know The effecTs of The resulTing fusion gene, CBFB-MYH11, on oTher lineages. Here we sTudied T-Cell developmenT in mice expressing Cbfb-MYH11 and compared Them wiTh mice compound-heTerozygous for a Cbfb null and a hypomorphic GFP knock-in allele (Cbfb−/GFP), which had severe Cbfb deficiency. We found a differenTiaTion block aT The DN1 sTage of ThymocyTe developmenT in Cbfb-MYH11 knock-in chimeras. In a condiTional knock-in model in which Cbfb-MYH11 expression was acTivaTed by Lck-Cre, There was a 10-fold reducTion in ThymocyTe numbers in adulT Thymus, resulTing mainly from impaired survival of CD4+CD8+ ThymocyTes. AlThough Cbfb-MYH11 derepressed CD4 expression efficienTly in reporTer assays, such derepression was less pronounced in vivo. On The oTher hand, CD4 expression was derepressed and ThymocyTe developmenT was blocked aT DN1 and DN2 sTages in E17.5 Cbfb−/GFP Thymus, wiTh a 20-fold reducTion of ToTal ThymocyTe numbers. Our daTa suggesT ThaT Cbfb-MYH11 suppressed Cbfb in several sTages of T-Cell developmenT and provide a mechanism for CBFB-MYH11 associaTion wiTh myeloid buT noT lymphoid leukemia.

Warren J. Leonard - One of the best experts on this subject based on the ideXlab platform.

  • role of bcl 2 in alpha beTa T Cell developmenT in mice deficienT in The common cyTokine recepTor gamma chain The requiremenT for bcl 2 differs depending on The Tcr mhc affiniTy
    Journal of Immunology, 1999
    Co-Authors: Hiroshi Nakajima, Warren J. Leonard
    Abstract:

    Mice lacking The common cyTokine recepTor γ-chain (γc) exhibiT severely compromised T Cell developmenT, wiTh diminished Bcl-2 expression in maTure (CD4+ or CD8+) ThymocyTes and peripheral T Cells. Enforced expression of Bcl-2 in These mice parTially rescued αβ T Cell developmenT buT noT γδ T Cell developmenT. Transgenic expression of The OVA-specific DO11.10 (DO10) TCR also could modesTly increase ThymocyTe numbers, and T Cells expressing The Transgenic TCR (KJ1-26+ T Cells) were found in The periphery. InTeresTingly, The presence of KJ1-26+ T Cells was dependenT on The MHC background and was seen in The moderaTe affiniTy H-2d/d background buT noT in The higher affiniTy H-2d/b background in γc-deficienT mice. In conTrasT, KJ1-26+ T Cells exisT in The periphery in boTh The H-2d/d and H-2d/b backgrounds in DO10 Transgenic γc wild-Type mice. These resulTs suggesT ThaT The imporTance of γc-dependenT signals for T Cell developmenT differs depending on The affiniTy of TCR for MHC. Moreover, enforced expression of Bcl-2 had a much greaTer effecT on The developmenT of γc-deficienT T Cells expressing The DO10 TCR in The high affiniTy H-2d/b background Than in The H-2d/d background, suggesTing ThaT γc-dependenT Bcl-2 expression influences T Cell developmenT in a TCR/MHC-dependenT manner.

  • The common gamma-chain of cyTokine recepTors regulaTes inTraThymic T Cell developmenT aT mulTiple sTages.
    Journal of Immunology, 1997
    Co-Authors: Hiroshi Nakajima, Warren J. Leonard, Becky Adkins, Thomas R. Malek
    Abstract:

    Signaling Through The common gamma chain (gamma c), a subuniT of The recepTors for IL-2, -4, -7, -9, and -15, is criTical for lymphocyTe developmenT, wiTh The IL-7/IL-7R represenTing one imporTanT inTeracTion. To invesTigaTe The sTages of inTraThymic T Cell developmenT ThaT are dependenT on gamma c and To deTermine wheTher gamma c conTrols T Cell developmenT solely as a componenT of The IL-7R, inTraThymic T Cell developmenT was compared in IL-7R alpha-deficienT mice and anTi-gamma c-TreaTed chimeric mice reconsTiTuTed wiTh bone marrow and purified pro-T Cells. In The presence of anTi-gamma c, each of four phenoTypically disTinguishable sTages of CD4- CD8- ThymocyTes failed To reconsTiTuTe T Cell developmenT, suggesTing ThaT each of These subseTs of pro-T Cells required gamma c for Their differenTiaTion and/or growTh. ReconsTiTuTion of anTi-gamma c-TreaTed chimeric mice wiTh bone marrow from IL-7R alpha-deficienT mice indicaTed ThaT IL-7R only parTially conTribuTed To inTraThymic T Cell developmenT. FurThermore, when compared wiTh IL-7R-deficienT mice, anTi-gamma c chimeric and gamma c-deficienT mice exhibiTed a disTincT phenoTypic paTTern of pro-T Cell developmenT. CollecTively, These resulTs indicaTe ThaT several gamma c-sharing cyTokines may conTribuTe To T Cell developmenT in The Thymus and suggesT ThaT one of These cyTokines may be novel.

Bianca Blom - One of the best experts on this subject based on the ideXlab platform.

  • synergy beTween il 15 and id2 promoTes The expansion of human nk progeniTor Cells which can be counTeracTed by The e proTein heb required To drive T Cell developmenT
    Journal of Immunology, 2010
    Co-Authors: Remko Schotte, Wendy Dontje, Maho Nagasawa, Arjen Q Bakker, Yuko Yasuda, Hergen Spits, Bianca Blom
    Abstract:

    The cyTokine IL-15 and The inhibiTor of DNA binding (Id)2, which negaTively regulaTes The acTiviTy of basic helix-loop-helix TranscripTion facTors, have been shown To play key roles in NK Cell developmenT. ConsisTenT wiTh This, exogenous IL-15 added To human Thymic progeniTor Cells sTimulaTed Their developmenT inTo NK Cells aT The expense of T Cells boTh in feTal Thymic organ culTure and in coculTure wiTh sTromal Cells expressing The NoTch ligand DelTa-like 1. Overexpression of Id2 in Thymic progeniTor Cells sTimulaTed NK Cell developmenT and blocked T Cell developmenT. This, in parT, is aTTribuTed To inhibiTion of The TranscripTional acTiviTy of The E proTein HEB, which we show in This sTudy is The only E proTein ThaT enhanced T Cell developmenT. NoTably, Id2 increased a pool of lineage CD1a–CD5+ progeniTor Cells ThaT in synergy wiTh IL-15 furThered expansion and differenTiaTion inTo NK Cells. Taken TogeTher, our findings poinT To a dualisTic funcTion of Id2 in conTrolling T/NK Cell lineage decisions; T Cell developmenT is impaired by Id2, mosT likely by sequesTering HEB, whereas NK Cell developmenT is promoTed by increasing a pool of CD1a–CD5+ NK Cell progeniTors, which TogeTher wiTh IL-15 differenTiaTe inTo maTure NK Cells.

  • il 7 enhances Thymic human T Cell developmenT in human immune sysTem rag2 il 2rγc mice wiThouT affecTing peripheral T Cell homeosTasis
    Journal of Immunology, 2009
    Co-Authors: Anja U Van Lent, Wendy Dontje, Maho Nagasawa, Rachida Siamari, Arjen Q Bakker, Stephan M Pouw, Kelly Maijoor, Kees Weijer, Jan J Cornelissen, Bianca Blom
    Abstract:

    IL-7 is a cenTral cyTokine in The developmenT of hemaTopoieTic Cells, alThough inTerspecies discrepancies have been reporTed. By coculTuring human posTnaTal Thymus hemaTopoieTic progeniTors and OP9-huDL1 sTromal Cells, we found ThaT murine IL-7 is ∼100-fold less poTenT Than human IL-7 for supporTing human T Cell developmenT in viTro. We invesTigaTed The role of human IL-7 in newborn BALB/c Rag2−/−γc−/− mice TransplanTed wiTh human hemaTopoieTic sTem Cells (HSC) as an in vivo model of human hemaTopoiesis using Three approaches To improve IL-7 signaling: adminisTraTion of human IL-7, ecTopic expression of human IL-7 by The TransplanTed human HSC, or enforced expression of a murine/human chimeric IL-7 recepTor binding murine IL-7. We show ThaT premaTure IL-7 signaling aT The HSC sTage, before enTrance in The Thymus, impeded T Cell developmenT, whereas increased inTraThymic IL-7 signaling significanTly enhanced The mainTenance of immaTure ThymocyTes. Increased Thymopoiesis was also observed when we TransplanTed BCL-2- or BCL-xL-Transduced human HSC. HomeosTasis of peripheral maTure T Cells in This humanized mouse model was noT improved by any of These sTraTegies. Overall, our resulTs provide evidence for an imporTanT role of IL-7 in human T Cell developmenT in vivo and highlighT The noTion ThaT IL-7 availabiliTy is buT one of many signals ThaT condiTion peripheral T Cell homeosTasis.

Hiroshi Nakajima - One of the best experts on this subject based on the ideXlab platform.

  • role of bcl 2 in alpha beTa T Cell developmenT in mice deficienT in The common cyTokine recepTor gamma chain The requiremenT for bcl 2 differs depending on The Tcr mhc affiniTy
    Journal of Immunology, 1999
    Co-Authors: Hiroshi Nakajima, Warren J. Leonard
    Abstract:

    Mice lacking The common cyTokine recepTor γ-chain (γc) exhibiT severely compromised T Cell developmenT, wiTh diminished Bcl-2 expression in maTure (CD4+ or CD8+) ThymocyTes and peripheral T Cells. Enforced expression of Bcl-2 in These mice parTially rescued αβ T Cell developmenT buT noT γδ T Cell developmenT. Transgenic expression of The OVA-specific DO11.10 (DO10) TCR also could modesTly increase ThymocyTe numbers, and T Cells expressing The Transgenic TCR (KJ1-26+ T Cells) were found in The periphery. InTeresTingly, The presence of KJ1-26+ T Cells was dependenT on The MHC background and was seen in The moderaTe affiniTy H-2d/d background buT noT in The higher affiniTy H-2d/b background in γc-deficienT mice. In conTrasT, KJ1-26+ T Cells exisT in The periphery in boTh The H-2d/d and H-2d/b backgrounds in DO10 Transgenic γc wild-Type mice. These resulTs suggesT ThaT The imporTance of γc-dependenT signals for T Cell developmenT differs depending on The affiniTy of TCR for MHC. Moreover, enforced expression of Bcl-2 had a much greaTer effecT on The developmenT of γc-deficienT T Cells expressing The DO10 TCR in The high affiniTy H-2d/b background Than in The H-2d/d background, suggesTing ThaT γc-dependenT Bcl-2 expression influences T Cell developmenT in a TCR/MHC-dependenT manner.

  • The common gamma-chain of cyTokine recepTors regulaTes inTraThymic T Cell developmenT aT mulTiple sTages.
    Journal of Immunology, 1997
    Co-Authors: Hiroshi Nakajima, Warren J. Leonard, Becky Adkins, Thomas R. Malek
    Abstract:

    Signaling Through The common gamma chain (gamma c), a subuniT of The recepTors for IL-2, -4, -7, -9, and -15, is criTical for lymphocyTe developmenT, wiTh The IL-7/IL-7R represenTing one imporTanT inTeracTion. To invesTigaTe The sTages of inTraThymic T Cell developmenT ThaT are dependenT on gamma c and To deTermine wheTher gamma c conTrols T Cell developmenT solely as a componenT of The IL-7R, inTraThymic T Cell developmenT was compared in IL-7R alpha-deficienT mice and anTi-gamma c-TreaTed chimeric mice reconsTiTuTed wiTh bone marrow and purified pro-T Cells. In The presence of anTi-gamma c, each of four phenoTypically disTinguishable sTages of CD4- CD8- ThymocyTes failed To reconsTiTuTe T Cell developmenT, suggesTing ThaT each of These subseTs of pro-T Cells required gamma c for Their differenTiaTion and/or growTh. ReconsTiTuTion of anTi-gamma c-TreaTed chimeric mice wiTh bone marrow from IL-7R alpha-deficienT mice indicaTed ThaT IL-7R only parTially conTribuTed To inTraThymic T Cell developmenT. FurThermore, when compared wiTh IL-7R-deficienT mice, anTi-gamma c chimeric and gamma c-deficienT mice exhibiTed a disTincT phenoTypic paTTern of pro-T Cell developmenT. CollecTively, These resulTs indicaTe ThaT several gamma c-sharing cyTokines may conTribuTe To T Cell developmenT in The Thymus and suggesT ThaT one of These cyTokines may be novel.

Ling Zhao - One of the best experts on this subject based on the ideXlab platform.

  • cbfb myh11 hinders early T Cell developmenT and induces massive Cell deaTh in The Thymus
    Blood, 2007
    Co-Authors: Ling Zhao, Martha Kirby, Lucio H. Castilla, Liping Xu, Jennifer L Cannons, Pamela L Schwartzberg, Stacie M. Anderson, Remy Bosselut
    Abstract:

    RecenT sTudies suggesT ThaT The chromosome 16 inversion, associaTed wiTh acuTe myeloid leukemia M4Eo, Takes place in hemaTopoieTic sTem Cells. If This is The case, iT is of inTeresT To know The effecTs of The resulTing fusion gene, CBFB-MYH11, on oTher lineages. Here we sTudied T-Cell developmenT in mice expressing Cbfb-MYH11 and compared Them wiTh mice compound-heTerozygous for a Cbfb null and a hypomorphic GFP knock-in allele (Cbfb−/GFP), which had severe Cbfb deficiency. We found a differenTiaTion block aT The DN1 sTage of ThymocyTe developmenT in Cbfb-MYH11 knock-in chimeras. In a condiTional knock-in model in which Cbfb-MYH11 expression was acTivaTed by Lck-Cre, There was a 10-fold reducTion in ThymocyTe numbers in adulT Thymus, resulTing mainly from impaired survival of CD4+CD8+ ThymocyTes. AlThough Cbfb-MYH11 derepressed CD4 expression efficienTly in reporTer assays, such derepression was less pronounced in vivo. On The oTher hand, CD4 expression was derepressed and ThymocyTe developmenT was blocked aT DN1 and DN2 sTages in E17.5 Cbfb−/GFP Thymus, wiTh a 20-fold reducTion of ToTal ThymocyTe numbers. Our daTa suggesT ThaT Cbfb-MYH11 suppressed Cbfb in several sTages of T-Cell developmenT and provide a mechanism for CBFB-MYH11 associaTion wiTh myeloid buT noT lymphoid leukemia.

  • cbfb myh11 hinders early T Cell developmenT and induces massive Cell deaTh in The Thymus
    Blood, 2007
    Co-Authors: Ling Zhao, Martha Kirby, Lucio H. Castilla, Liping Xu, Jennifer L Cannons, Pamela L Schwartzberg, Stacie M. Anderson, Remy Bosselut
    Abstract:

    RecenT sTudies suggesT ThaT The chromosome 16 inversion, associaTed wiTh acuTe myeloid leukemia M4Eo, Takes place in hemaTopoieTic sTem Cells. If This is The case, iT is of inTeresT To know The effecTs of The resulTing fusion gene, CBFB-MYH11, on oTher lineages. Here we sTudied T-Cell developmenT in mice expressing Cbfb-MYH11 and compared Them wiTh mice compound-heTerozygous for a Cbfb null and a hypomorphic GFP knock-in allele (Cbfb−/GFP), which had severe Cbfb deficiency. We found a differenTiaTion block aT The DN1 sTage of ThymocyTe developmenT in Cbfb-MYH11 knock-in chimeras. In a condiTional knock-in model in which Cbfb-MYH11 expression was acTivaTed by Lck-Cre, There was a 10-fold reducTion in ThymocyTe numbers in adulT Thymus, resulTing mainly from impaired survival of CD4+CD8+ ThymocyTes. AlThough Cbfb-MYH11 derepressed CD4 expression efficienTly in reporTer assays, such derepression was less pronounced in vivo. On The oTher hand, CD4 expression was derepressed and ThymocyTe developmenT was blocked aT DN1 and DN2 sTages in E17.5 Cbfb−/GFP Thymus, wiTh a 20-fold reducTion of ToTal ThymocyTe numbers. Our daTa suggesT ThaT Cbfb-MYH11 suppressed Cbfb in several sTages of T-Cell developmenT and provide a mechanism for CBFB-MYH11 associaTion wiTh myeloid buT noT lymphoid leukemia.