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  1. Article ; Online: Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells

    Seung-Chul Choi / Anton A. Titov / Georges Abboud / Howard R. Seay / Todd M. Brusko / Derry C. Roopenian / Shahram Salek-Ardakani / Laurence Morel

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 13

    Abstract: T cell functions depend on distinct metabolic fluxes. Here the authors show different metabolic requirements of humoral responses to self versus microbial antigens: while glucose is dispensable for antiviral Tfh and antibody responses, it is essential to ...

    Abstract T cell functions depend on distinct metabolic fluxes. Here the authors show different metabolic requirements of humoral responses to self versus microbial antigens: while glucose is dispensable for antiviral Tfh and antibody responses, it is essential to mount these responses against autoantigens.
    Keywords Science ; Q
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Inhibition of glucose metabolism selectively targets autoreactive follicular helper T cells

    Seung-Chul Choi / Anton A. Titov / Georges Abboud / Howard R. Seay / Todd M. Brusko / Derry C. Roopenian / Shahram Salek-Ardakani / Laurence Morel

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 13

    Abstract: T cell functions depend on distinct metabolic fluxes. Here the authors show different metabolic requirements of humoral responses to self versus microbial antigens: while glucose is dispensable for antiviral Tfh and antibody responses, it is essential to ...

    Abstract T cell functions depend on distinct metabolic fluxes. Here the authors show different metabolic requirements of humoral responses to self versus microbial antigens: while glucose is dispensable for antiviral Tfh and antibody responses, it is essential to mount these responses against autoantigens.
    Keywords Science ; Q
    Language English
    Publishing date 2018-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Ligand-Blocking and Membrane-Proximal Domain Targeting Anti-OX40 Antibodies Mediate Potent T Cell-Stimulatory and Anti-Tumor Activity

    Pamela Zhang / Guang Huan Tu / Jie Wei / Pamela Santiago / Lance R. Larrabee / Sindy Liao-Chan / Tina Mistry / Matthew Ling-Hon Chu / Tao Sai / Kevin Lindquist / Hua Long / Javier Chaparro-Riggers / Shahram Salek-Ardakani / Yik Andy Yeung

    Cell Reports, Vol 27, Iss 11, Pp 3117-3123.e

    2019  Volume 5

    Abstract: Summary: Agonistic antibodies targeting the tumor necrosis factor (TNF) superfamily of co-stimulatory receptors (TNFRSF) are progressing through various stages of clinical development for cancer treatment, but the desired and defining features of these ... ...

    Abstract Summary: Agonistic antibodies targeting the tumor necrosis factor (TNF) superfamily of co-stimulatory receptors (TNFRSF) are progressing through various stages of clinical development for cancer treatment, but the desired and defining features of these agents for optimal biological activity remain controversial. One idea, based on recent studies with CD40, is that non-ligand-blocking antibodies targeting membrane-distal cysteine-rich domain 1 (CRD1) have superior agonistic activities compared with ligand-blocking antibodies targeting more membrane-proximal CRDs. Here, we determined the binding and functional characteristics of a panel of antibodies targeting CRDs 1–4 of OX40 (also known as TNFRSF4 or CD134). In striking contrast to CD40, we found that ligand-blocking CRD2-binding and membrane-proximal CRD4-binding anti-OX40 antibodies have the strongest agonistic and anti-tumor activities. These findings have important translational implications and further highlight that the relationship between epitope specificity and agonistic activity will be an important issue to resolve on a case-by-case basis when optimizing antibodies targeting different co-stimulatory tumor necrosis factor receptors (TNFRs). : Epitope specificity is an important consideration when designing anti-TNFR agonistic antibodies for cancer treatment. Zhang et al. identify a new panel of antibodies targeting CRDs 1–4 of OX40 and show that ligand-blocking CRD2-binding and membrane-proximal CRD4-binding anti-OX40 antibodies have the strongest agonistic and anti-tumor activities. Keywords: OX40, agonist, monoclonal antibody, epitope, TNFR, OX86, ligand-blocking, membrane-proximal
    Keywords Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2019-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab

    S. Michael Chin / Christopher R. Kimberlin / Zygy Roe-Zurz / Pamela Zhang / Allison Xu / Sindy Liao-Chan / Debasish Sen / Andrew R. Nager / Nicole Schirle Oakdale / Colleen Brown / Feng Wang / Yuting Yang / Kevin Lindquist / Yik Andy Yeung / Shahram Salek-Ardakani / Javier Chaparro-Riggers

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 13

    Abstract: The costimulatory T-cell receptor 4-1BB is an immuno-oncology target. Here the authors present the ligand bound 4-1BB receptor crystal structure in addition to the structures of 4-1BB bound with two therapeutic antibodies and verify the antibody binding ... ...

    Abstract The costimulatory T-cell receptor 4-1BB is an immuno-oncology target. Here the authors present the ligand bound 4-1BB receptor crystal structure in addition to the structures of 4-1BB bound with two therapeutic antibodies and verify the antibody binding sites by mutational analysis, which is of interest for further 4-1BB therapeutics development.
    Keywords Science ; Q
    Language English
    Publishing date 2018-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Structure of the 4-1BB/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab

    S. Michael Chin / Christopher R. Kimberlin / Zygy Roe-Zurz / Pamela Zhang / Allison Xu / Sindy Liao-Chan / Debasish Sen / Andrew R. Nager / Nicole Schirle Oakdale / Colleen Brown / Feng Wang / Yuting Yang / Kevin Lindquist / Yik Andy Yeung / Shahram Salek-Ardakani / Javier Chaparro-Riggers

    Nature Communications, Vol 9, Iss 1, Pp 1-

    2018  Volume 13

    Abstract: The costimulatory T-cell receptor 4-1BB is an immuno-oncology target. Here the authors present the ligand bound 4-1BB receptor crystal structure in addition to the structures of 4-1BB bound with two therapeutic antibodies and verify the antibody binding ... ...

    Abstract The costimulatory T-cell receptor 4-1BB is an immuno-oncology target. Here the authors present the ligand bound 4-1BB receptor crystal structure in addition to the structures of 4-1BB bound with two therapeutic antibodies and verify the antibody binding sites by mutational analysis, which is of interest for further 4-1BB therapeutics development.
    Keywords Science ; Q
    Language English
    Publishing date 2018-11-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

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  6. Article ; Online: CD8 T cell memory to a viral pathogen requires trans cosignaling between HVEM and BTLA.

    Rachel Flynn / Tarun Hutchinson / Kenneth M Murphy / Carl F Ware / Michael Croft / Shahram Salek-Ardakani

    PLoS ONE, Vol 8, Iss 10, p e

    2013  Volume 77991

    Abstract: Defining the molecular interactions required to program activated CD8 T cells to survive and become memory cells may allow us to understand how to augment anti-viral immunity. HVEM (herpes virus entry mediator) is a member of the tumor necrosis factor ... ...

    Abstract Defining the molecular interactions required to program activated CD8 T cells to survive and become memory cells may allow us to understand how to augment anti-viral immunity. HVEM (herpes virus entry mediator) is a member of the tumor necrosis factor receptor (TNFR) family that interacts with ligands in the TNF family, LIGHT and Lymphotoxin-α, and in the Ig family, B and T lymphocyte attenuator (BTLA) and CD160. The Ig family members initiate inhibitory signaling when engaged with HVEM, but may also activate survival gene expression. Using a model of vaccinia virus infection, we made the unexpected finding that deficiency in HVEM or BTLA profoundly impaired effector CD8 T cell survival and development of protective immune memory. Mixed adoptive transfer experiments indicated that BTLA expressed in CD8α+ dendritic cells functions as a trans-activating ligand that delivers positive co-signals through HVEM expressed in T cells. Our data demonstrate a critical role of HVEM-BTLA bidirectional cosignaling system in antiviral defenses by driving the differentiation of memory CD8 T cells.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: C-Myc regulation by costimulatory signals modulates the generation of CD8+ memory T cells during viral infection

    Mohammad Haque / Jianyong Song / Kristin Fino / Youfei Wang / Praneet Sandhu / Xinmeng Song / Christopher Norbury / Bing Ni / Deyu Fang / Shahram Salek-Ardakani / Jianxun Song

    Open Biology, Vol 6, Iss

    2016  Volume 1

    Abstract: The signalling mechanisms of costimulation in the development of memory T cells remain to be clarified. Here, we show that the transcription factor c-Myc in CD8+ T cells is controlled by costimulatory molecules, which modulates the development of memory ... ...

    Abstract The signalling mechanisms of costimulation in the development of memory T cells remain to be clarified. Here, we show that the transcription factor c-Myc in CD8+ T cells is controlled by costimulatory molecules, which modulates the development of memory CD8+ T cells. C-Myc expression was dramatically reduced in Cd28−/− or Ox40−/− memory CD8+ T cells, and c-Myc over-expression substantially reversed the defects in the development of T-cell memory following viral infection. C-Myc regulated the expression of survivin, an inhibitor of apoptosis, which promoted the generation of virus-specific memory CD8+ T cells. Moreover, over-expression of survivin with bcl-xL, a downstream molecule of NF-κB and intracellular target of costimulation that controls survival, in Cd28−/− or Ox40−/− CD8+ T cells, reversed the defects in the generation of memory T cells in response to viral infection. These results identify c-Myc as a key controller of memory CD8+ T cells from costimulatory signals.
    Keywords c-myc ; costimulation ; cd8+ t cells ; memory ; viral infection ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher The Royal Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: OX40 facilitates control of a persistent virus infection.

    Tobias Boettler / Friedrich Moeckel / Yang Cheng / Maximilian Heeg / Shahram Salek-Ardakani / Shane Crotty / Michael Croft / Matthias G von Herrath

    PLoS Pathogens, Vol 8, Iss 9, p e

    2012  Volume 1002913

    Abstract: During acute viral infections, clearance of the pathogen is followed by the contraction of the anti-viral T cell compartment. In contrast, T cell responses need to be maintained over a longer period of time during chronic viral infections in order to ... ...

    Abstract During acute viral infections, clearance of the pathogen is followed by the contraction of the anti-viral T cell compartment. In contrast, T cell responses need to be maintained over a longer period of time during chronic viral infections in order to control viral replication and to avoid viral spreading. Much is known about inhibitory signals such as through PD-1 that limit T cell activity during chronic viral infection, but little is known about the stimulatory signals that allow maintenance of anti-viral T cells. Here, we show that the co-stimulatory molecule OX40 (CD134) is critically required in the context of persistent LCMV clone 13 infection. Anti-viral T cells express high levels of OX40 in the presence of their cognate antigen and T cells lacking the OX40 receptor fail to accumulate sufficiently. Moreover, the emergence of T cell dependent germinal center responses and LCMV-specific antibodies are severely impaired. Consequently, OX40-deficient mice fail to control LCMV clone 13 infection over time, highlighting the importance of this signaling pathway during persistent viral infection.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2012-09-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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