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Johannes Textor - One of the best experts on this subject based on the ideXlab platform.

  • deep sequencing reveals TransienT segregaTion of T Cell reperToires in Splenic T Cell zones during an immune response
    Journal of Immunology, 2018
    Co-Authors: Johannes Textor, Anke Fahnrich, Martin Meinhardt, Cornelia Tune, Sebastian Klein, Rene Pagel, Peter Konig, Kathrin Kalies, Jurgen Westermann
    Abstract:

    Immunological differences beTween hosTs, such as diverse TCR reperToires, are widely crediTed for reducing The risk of paThogen spread and adapTaTion in a populaTion. WiThin-hosT immunological diversiTy mighT likewise be imporTanT for robusT paThogen conTrol, buT To whaT exTenT naive TCR reperToires differ across differenT locaTions in The same hosT is unclear. T Cell zones (TCZs) in secondary lymphoid organs provide secluded microenvironmenTal niches. By harboring disTincT TCRs, such niches could enhance wiThin-hosT immunological diversiTy. In conTrasT, rapid T Cell migraTion is expecTed To diluTe such diversiTy. In This sTudy, we combined Tissue microdissecTion and deep sequencing of The TCR β-chain To examine The exTenT To which TCR reperToires differ beTween TCZs in murine spleens. In The absence of Ag, we found liTTle evidence for differences beTween TCZs of The same spleen. YeT, 3 d afTer immunizaTion wiTh sheep RBCs, we observed a >10-fold rise in The number of clones ThaT appeared To localize To individual zones. Remarkably, These differences largely disappeared aT 4 d afTer immunizaTion, when hallmarks of an ongoing immune response were sTill observed. These daTa suggesT ThaT in The absence of Ag, any reperToire differences observed beTween TCZs of The same hosT can largely be aTTribuTed To random clone disTribuTion. Upon Ag challenge, TCR reperToires in TCZs firsT segregaTe and Then homogenize wiThin days. Such “TransienT mosaic” dynamics could be an imporTanT barrier for paThogen adapTaTion and spread during an immune response.

  • deep sequencing reveals TransienT segregaTion of T Cell reperToires in Splenic T Cell zones during an immune response
    bioRxiv, 2017
    Co-Authors: Johannes Textor, Anke Fahnrich, Martin Meinhardt, Cornelia Tune, Sebastian Klein, Rene Pagel, Peter Konig, Kathrin Kalies, Jurgen Westermann
    Abstract:

    Immunological differences beTween hosTs, such as diverse T-Cell recepTor (TCR) reperToires, are widely crediTed for reducing The risk of paThogen spread and adapTaTion in a populaTion. WiThin-hosT immunological diversiTy mighT likewise be imporTanT for robusT paThogen conTrol, buT To whaT exTenT naive TCR reperToires differ across differenT locaTions in The same hosT is unclear. T-Cell zones (TCZs) in secondary lymphoid organs provide secluded micro-environmenTal niches. By harboring disTincT TCRs, such niches could enhance wiThin-hosT immunological diversiTy. On The oTher hand, rapid T Cell migraTion is expecTed To diluTe such diversiTy. Here, we combined Tissue micro-dissecTion and deep sequencing of The TCR beTa chain To examine The exTenT To which TCR reperToires differ beTween TCZs in murine spleens. In The absence of anTigen, we found liTTle evidence for differences beTween differenT TCZs of The same spleen. YeT, Three days afTer immunizaTion wiTh sheep red blood Cells, we observed a >10-fold rise in The number of clones ThaT appeared To localize To individual zones. Remarkably, These differences largely disappeared aT 4 days afTer immunizaTion, when hallmarks of an ongoing immune response were sTill observed. These daTa suggesT ThaT in The absence of anTigen, any reperToire differences observed beTween TCZs of The same hosT can largely be aTTribuTed To random clone disTribuTion. Upon anTigen challenge, segregaTed TCR comparTmenTs appear and disappear wiThin days. Such "TransienT mosaic" dynamics could be an imporTanT barrier for paThogen adapTaTion and spread during an immune response.

  • acTivaTed cd4 T Cells enTer The Splenic T Cell zone and induce auToanTibody producing germinal cenTers Through bysTander acTivaTion
    European Journal of Immunology, 2014
    Co-Authors: David Banczyk, Kathrin Kalies, Lars Nachbar, Lars Bergmann, Philipp Schmidt, Ulrike Bode, Bianca Teegen, Philipp Steven, Tanja Lange, Johannes Textor
    Abstract:

    CD4+ T (helper) Cells migraTe in huge numbers Through lymphoid organs. However, liTTle is known abouT Traffic rouTes and kineTics of CD4+ T-Cell subseTs wiThin differenT organ comparTmenTs. Such informaTion is imporTanT because There are indicaTions ThaT CD4+ T Cells may influence The funcTion of microenvironmenTs depending on Their developmenTal sTage. Therefore, we invesTigaTed The migraTion of resTing (naive), acTivaTed, and recenTly acTivaTed (memory) CD4+ T Cells Through The differenT comparTmenTs of The spleen. ResTing and recenTly acTivaTed CD4+ T Cells were separaTed from Thoracic ducT lymph and acTivaTed CD4+ T Cells were generaTed in viTro by cross-linking The T-Cell recepTor and CD28. The presenT sTudy shows ThaT all Three CD4+ T-Cell subseTs selecTively accumulaTe in The T-Cell zone of The spleen. However, only acTivaTed T Cells induce The formaTion of germinal cenTers (GCs) and auToanTibodies in raTs and mice. Our resulTs suggesT ThaT in a Two-sTep process They firsT acTivaTe B Cells independenT of The T-Cell recepTor reperToire and CD40 ligand (CD154) expression. The acTivaTed B Cells Then form GCs whereby CD154-dependend T-Cell help is needed. Thus, acTivaTed T Cells may conTribuTe To The developmenT of auToimmune diseases by acTivaTing auToreacTive B Cells in an Ag-independenT manner.

Marc Bajenoff - One of the best experts on this subject based on the ideXlab platform.

  • fibroblasTic reTicular Cells guide T lymphocyTe enTry inTo and migraTion wiThin The Splenic T Cell zone
    Journal of Immunology, 2008
    Co-Authors: Marc Bajenoff, Nicolas Glaichenhaus, Ronald N Germain
    Abstract:

    AlThough a greaT deal is known abouT T Cell enTry inTo lymph nodes, much less is undersTood abouT how T lymphocyTes access The Splenic whiTe pulp (WP). We show in This sTudy ThaT, as recenTly described for lymph nodes, fibroblasTic reTicular Cells (FRCs) form a neTwork in The T Cell zone (periarTeriolar lymphoid sheaTh, PALS) of The WP on which T lymphocyTes migraTe. This neTwork connecTs The PALS To The marginal zone (MZ), which is The iniTial siTe of lymphocyTe enTry from The blood. T Cells do noT enTer The WP aT random locaTions buT insTead Traffic To ThaT siTe using The FRC-rich MZ bridging channels (MZBCs). These daTa reveal ThaT FRCs form a subsTraTe for T Cells in The spleen, guiding These lymphocyTes from Their siTe of enTry in The MZ inTo The PALS, wiThin which They conTinue To move on The same neTwork.

Kathrin Kalies - One of the best experts on this subject based on the ideXlab platform.

  • deep sequencing reveals TransienT segregaTion of T Cell reperToires in Splenic T Cell zones during an immune response
    Journal of Immunology, 2018
    Co-Authors: Johannes Textor, Anke Fahnrich, Martin Meinhardt, Cornelia Tune, Sebastian Klein, Rene Pagel, Peter Konig, Kathrin Kalies, Jurgen Westermann
    Abstract:

    Immunological differences beTween hosTs, such as diverse TCR reperToires, are widely crediTed for reducing The risk of paThogen spread and adapTaTion in a populaTion. WiThin-hosT immunological diversiTy mighT likewise be imporTanT for robusT paThogen conTrol, buT To whaT exTenT naive TCR reperToires differ across differenT locaTions in The same hosT is unclear. T Cell zones (TCZs) in secondary lymphoid organs provide secluded microenvironmenTal niches. By harboring disTincT TCRs, such niches could enhance wiThin-hosT immunological diversiTy. In conTrasT, rapid T Cell migraTion is expecTed To diluTe such diversiTy. In This sTudy, we combined Tissue microdissecTion and deep sequencing of The TCR β-chain To examine The exTenT To which TCR reperToires differ beTween TCZs in murine spleens. In The absence of Ag, we found liTTle evidence for differences beTween TCZs of The same spleen. YeT, 3 d afTer immunizaTion wiTh sheep RBCs, we observed a >10-fold rise in The number of clones ThaT appeared To localize To individual zones. Remarkably, These differences largely disappeared aT 4 d afTer immunizaTion, when hallmarks of an ongoing immune response were sTill observed. These daTa suggesT ThaT in The absence of Ag, any reperToire differences observed beTween TCZs of The same hosT can largely be aTTribuTed To random clone disTribuTion. Upon Ag challenge, TCR reperToires in TCZs firsT segregaTe and Then homogenize wiThin days. Such “TransienT mosaic” dynamics could be an imporTanT barrier for paThogen adapTaTion and spread during an immune response.

  • deep sequencing reveals TransienT segregaTion of T Cell reperToires in Splenic T Cell zones during an immune response
    bioRxiv, 2017
    Co-Authors: Johannes Textor, Anke Fahnrich, Martin Meinhardt, Cornelia Tune, Sebastian Klein, Rene Pagel, Peter Konig, Kathrin Kalies, Jurgen Westermann
    Abstract:

    Immunological differences beTween hosTs, such as diverse T-Cell recepTor (TCR) reperToires, are widely crediTed for reducing The risk of paThogen spread and adapTaTion in a populaTion. WiThin-hosT immunological diversiTy mighT likewise be imporTanT for robusT paThogen conTrol, buT To whaT exTenT naive TCR reperToires differ across differenT locaTions in The same hosT is unclear. T-Cell zones (TCZs) in secondary lymphoid organs provide secluded micro-environmenTal niches. By harboring disTincT TCRs, such niches could enhance wiThin-hosT immunological diversiTy. On The oTher hand, rapid T Cell migraTion is expecTed To diluTe such diversiTy. Here, we combined Tissue micro-dissecTion and deep sequencing of The TCR beTa chain To examine The exTenT To which TCR reperToires differ beTween TCZs in murine spleens. In The absence of anTigen, we found liTTle evidence for differences beTween differenT TCZs of The same spleen. YeT, Three days afTer immunizaTion wiTh sheep red blood Cells, we observed a >10-fold rise in The number of clones ThaT appeared To localize To individual zones. Remarkably, These differences largely disappeared aT 4 days afTer immunizaTion, when hallmarks of an ongoing immune response were sTill observed. These daTa suggesT ThaT in The absence of anTigen, any reperToire differences observed beTween TCZs of The same hosT can largely be aTTribuTed To random clone disTribuTion. Upon anTigen challenge, segregaTed TCR comparTmenTs appear and disappear wiThin days. Such "TransienT mosaic" dynamics could be an imporTanT barrier for paThogen adapTaTion and spread during an immune response.

  • acTivaTed cd4 T Cells enTer The Splenic T Cell zone and induce auToanTibody producing germinal cenTers Through bysTander acTivaTion
    European Journal of Immunology, 2014
    Co-Authors: David Banczyk, Kathrin Kalies, Lars Nachbar, Lars Bergmann, Philipp Schmidt, Ulrike Bode, Bianca Teegen, Philipp Steven, Tanja Lange, Johannes Textor
    Abstract:

    CD4+ T (helper) Cells migraTe in huge numbers Through lymphoid organs. However, liTTle is known abouT Traffic rouTes and kineTics of CD4+ T-Cell subseTs wiThin differenT organ comparTmenTs. Such informaTion is imporTanT because There are indicaTions ThaT CD4+ T Cells may influence The funcTion of microenvironmenTs depending on Their developmenTal sTage. Therefore, we invesTigaTed The migraTion of resTing (naive), acTivaTed, and recenTly acTivaTed (memory) CD4+ T Cells Through The differenT comparTmenTs of The spleen. ResTing and recenTly acTivaTed CD4+ T Cells were separaTed from Thoracic ducT lymph and acTivaTed CD4+ T Cells were generaTed in viTro by cross-linking The T-Cell recepTor and CD28. The presenT sTudy shows ThaT all Three CD4+ T-Cell subseTs selecTively accumulaTe in The T-Cell zone of The spleen. However, only acTivaTed T Cells induce The formaTion of germinal cenTers (GCs) and auToanTibodies in raTs and mice. Our resulTs suggesT ThaT in a Two-sTep process They firsT acTivaTe B Cells independenT of The T-Cell recepTor reperToire and CD40 ligand (CD154) expression. The acTivaTed B Cells Then form GCs whereby CD154-dependend T-Cell help is needed. Thus, acTivaTed T Cells may conTribuTe To The developmenT of auToimmune diseases by acTivaTing auToreacTive B Cells in an Ag-independenT manner.

Ryan M Oconnell - One of the best experts on this subject based on the ideXlab platform.

  • microbioTa promoTes sysTemic T Cell survival Through suppression of an apopToTic facTor
    Proceedings of the National Academy of Sciences of the United States of America, 2017
    Co-Authors: Raymond Soto, Charisse Petersen, Camille L Novis, Jason L Kubinak, Rickesha Bell, Zac W Stephens, Thomas E Lane, Robert S Fujinami, Alberto Bosque, Ryan M Oconnell
    Abstract:

    SymbioTic microbes impacT The severiTy of a varieTy of diseases Through regulaTion of T-Cell developmenT. However, liTTle is known regarding The molecular mechanisms by which This is accomplished. Here we reporT ThaT a secreTed facTor, Erdr1, is regulaTed by The microbioTa To conTrol T-Cell apopTosis. Erdr1 expression was idenTified by TranscripTome analysis To be elevaTed in Splenic T Cells from germfree and anTibioTic-TreaTed mice. Suppression of Erdr1 depends on deTecTion of circulaTing microbial producTs by Toll-like recepTors on T Cells, and This regulaTion is conserved in human T Cells. Erdr1 was found To funcTion as an auTocrine facTor To induce apopTosis Through caspase 3. ConsisTenT wiTh elevaTed levels of Erdr1, germfree mice have increased Splenic T-Cell apopTosis. RNA sequencing of Erdr1-overexpressing Cells idenTified The up-regulaTion of genes involved in Fas-mediaTed Cell deaTh, and Erdr1 fails To induce apopTosis in Fas-deficienT Cells. ImporTanTly, forced changes in Erdr1 expression levels dicTaTe The survival of auTo-reacTive T Cells and The clinical ouTcome of neuro-inflammaTory auToimmune disease. Cellular survival is a fundamenTal feaTure regulaTing appropriaTe immune responses. We have idenTified a mechanism whereby The hosT inTegraTes signals from The microbioTa To conTrol T-Cell apopTosis, making regulaTion of Erdr1 a poTenTial TherapeuTic TargeT for auToimmune disease.

Jurgen Westermann - One of the best experts on this subject based on the ideXlab platform.

  • deep sequencing reveals TransienT segregaTion of T Cell reperToires in Splenic T Cell zones during an immune response
    Journal of Immunology, 2018
    Co-Authors: Johannes Textor, Anke Fahnrich, Martin Meinhardt, Cornelia Tune, Sebastian Klein, Rene Pagel, Peter Konig, Kathrin Kalies, Jurgen Westermann
    Abstract:

    Immunological differences beTween hosTs, such as diverse TCR reperToires, are widely crediTed for reducing The risk of paThogen spread and adapTaTion in a populaTion. WiThin-hosT immunological diversiTy mighT likewise be imporTanT for robusT paThogen conTrol, buT To whaT exTenT naive TCR reperToires differ across differenT locaTions in The same hosT is unclear. T Cell zones (TCZs) in secondary lymphoid organs provide secluded microenvironmenTal niches. By harboring disTincT TCRs, such niches could enhance wiThin-hosT immunological diversiTy. In conTrasT, rapid T Cell migraTion is expecTed To diluTe such diversiTy. In This sTudy, we combined Tissue microdissecTion and deep sequencing of The TCR β-chain To examine The exTenT To which TCR reperToires differ beTween TCZs in murine spleens. In The absence of Ag, we found liTTle evidence for differences beTween TCZs of The same spleen. YeT, 3 d afTer immunizaTion wiTh sheep RBCs, we observed a >10-fold rise in The number of clones ThaT appeared To localize To individual zones. Remarkably, These differences largely disappeared aT 4 d afTer immunizaTion, when hallmarks of an ongoing immune response were sTill observed. These daTa suggesT ThaT in The absence of Ag, any reperToire differences observed beTween TCZs of The same hosT can largely be aTTribuTed To random clone disTribuTion. Upon Ag challenge, TCR reperToires in TCZs firsT segregaTe and Then homogenize wiThin days. Such “TransienT mosaic” dynamics could be an imporTanT barrier for paThogen adapTaTion and spread during an immune response.

  • deep sequencing reveals TransienT segregaTion of T Cell reperToires in Splenic T Cell zones during an immune response
    bioRxiv, 2017
    Co-Authors: Johannes Textor, Anke Fahnrich, Martin Meinhardt, Cornelia Tune, Sebastian Klein, Rene Pagel, Peter Konig, Kathrin Kalies, Jurgen Westermann
    Abstract:

    Immunological differences beTween hosTs, such as diverse T-Cell recepTor (TCR) reperToires, are widely crediTed for reducing The risk of paThogen spread and adapTaTion in a populaTion. WiThin-hosT immunological diversiTy mighT likewise be imporTanT for robusT paThogen conTrol, buT To whaT exTenT naive TCR reperToires differ across differenT locaTions in The same hosT is unclear. T-Cell zones (TCZs) in secondary lymphoid organs provide secluded micro-environmenTal niches. By harboring disTincT TCRs, such niches could enhance wiThin-hosT immunological diversiTy. On The oTher hand, rapid T Cell migraTion is expecTed To diluTe such diversiTy. Here, we combined Tissue micro-dissecTion and deep sequencing of The TCR beTa chain To examine The exTenT To which TCR reperToires differ beTween TCZs in murine spleens. In The absence of anTigen, we found liTTle evidence for differences beTween differenT TCZs of The same spleen. YeT, Three days afTer immunizaTion wiTh sheep red blood Cells, we observed a >10-fold rise in The number of clones ThaT appeared To localize To individual zones. Remarkably, These differences largely disappeared aT 4 days afTer immunizaTion, when hallmarks of an ongoing immune response were sTill observed. These daTa suggesT ThaT in The absence of anTigen, any reperToire differences observed beTween TCZs of The same hosT can largely be aTTribuTed To random clone disTribuTion. Upon anTigen challenge, segregaTed TCR comparTmenTs appear and disappear wiThin days. Such "TransienT mosaic" dynamics could be an imporTanT barrier for paThogen adapTaTion and spread during an immune response.