LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 10

Search options

  1. Article ; Online: A regulatory circuit controlled by extranuclear and nuclear retinoic acid receptor α determines T cell activation and function.

    Larange, Alexandre / Takazawa, Ikuo / Kakugawa, Kiyokazu / Thiault, Nicolas / Ngoi, SooMun / Olive, Meagan E / Iwaya, Hitoshi / Seguin, Laetitia / Vicente-Suarez, Ildefonso / Becart, Stephane / Verstichel, Greet / Balancio, Ann / Altman, Amnon / Chang, John T / Taniuchi, Ichiro / Lillemeier, Bjorn / Kronenberg, Mitchell / Myers, Samuel A / Cheroutre, Hilde

    Immunity

    2023  Volume 56, Issue 9, Page(s) 2054–2069.e10

    Abstract: Ligation of retinoic acid receptor alpha (RARα) by RA promotes varied transcriptional programs associated with immune activation and tolerance, but genetic deletion approaches suggest the impact of RARα on TCR signaling. Here, we examined whether RARα ... ...

    Abstract Ligation of retinoic acid receptor alpha (RARα) by RA promotes varied transcriptional programs associated with immune activation and tolerance, but genetic deletion approaches suggest the impact of RARα on TCR signaling. Here, we examined whether RARα would exert roles beyond transcriptional regulation. Specific deletion of the nuclear isoform of RARα revealed an RARα isoform in the cytoplasm of T cells. Extranuclear RARα was rapidly phosphorylated upon TCR stimulation and recruited to the TCR signalosome. RA interfered with extranuclear RARα signaling, causing suboptimal TCR activation while enhancing FOXP3
    MeSH term(s) Humans ; Retinoic Acid Receptor alpha/genetics ; Lymphocyte Activation ; Autoimmune Diseases ; Cell Membrane ; Receptors, Antigen, T-Cell
    Chemical Substances Retinoic Acid Receptor alpha ; Receptors, Antigen, T-Cell
    Language English
    Publishing date 2023-08-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1217235-2
    ISSN 1097-4180 ; 1074-7613
    ISSN (online) 1097-4180
    ISSN 1074-7613
    DOI 10.1016/j.immuni.2023.07.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: CD4

    Dicker, Martina / Li, Yingcong / Giles, Daniel A / Verstichel, Greet / Castelan, Viankail Cedillo / Ascui-Gac, Gabriel / Chou, Ting-Fang / Perez-Jeldres, Tamara / Cheroutre, Hilde / Kronenberg, Mitchell

    Frontiers in immunology

    2022  Volume 13, Page(s) 1034648

    Abstract: Colitis is characterized by an exacerbated intestinal immune response, but the genetic and other mechanisms regulating immune activation remain incompletely understood. In order to identify new pathways leading to colitis, we sought to identify genes ... ...

    Abstract Colitis is characterized by an exacerbated intestinal immune response, but the genetic and other mechanisms regulating immune activation remain incompletely understood. In order to identify new pathways leading to colitis, we sought to identify genes with increased expression in the colons of patients that also are near loci identified by genome wide association studies (GWAS) associated with IBD risk. One such SNP, rs9557195 was of particular interest because it is within an intron of
    MeSH term(s) Mice ; Humans ; Animals ; Dextran Sulfate/adverse effects ; Genome-Wide Association Study ; Mice, Inbred C57BL ; Colitis/chemically induced ; Colitis/genetics ; Disease Models, Animal ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/metabolism ; CD4-Positive T-Lymphocytes/metabolism
    Chemical Substances Dextran Sulfate (9042-14-2) ; Receptors, G-Protein-Coupled ; GPR183 protein, human ; GPR18 protein, human ; Gpr183 protein, mouse ; GPR18 protein, mouse
    Language English
    Publishing date 2022-10-28
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1034648
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Transcriptomes and metabolism define mouse and human MAIT cell populations.

    Chandra, Shilpi / Ascui, Gabriel / Riffelmacher, Thomas / Chawla, Ashu / Ramírez-Suástegui, Ciro / Castelan, Viankail C / Seumois, Gregory / Simon, Hayley / Murray, Mallory P / Seo, Goo-Young / Premlal, Ashmitaa L R / Schmiedel, Benjamin / Verstichel, Greet / Li, Yingcong / Lin, Chia-Hao / Greenbaum, Jason / Lamberti, John / Murthy, Raghav / Nigro, John /
    Cheroutre, Hilde / Ottensmeier, Christian H / Hedrick, Stephen M / Lu, Li-Fan / Vijayanand, Pandurangan / Kronenberg, Mitchell

    Science immunology

    2023  Volume 8, Issue 89, Page(s) eabn8531

    Abstract: Mucosal-associated invariant T (MAIT) cells are a subset of T lymphocytes that respond to microbial metabolites. We defined MAIT cell populations in different organs and characterized the developmental pathway of mouse and human MAIT cells in the thymus ... ...

    Abstract Mucosal-associated invariant T (MAIT) cells are a subset of T lymphocytes that respond to microbial metabolites. We defined MAIT cell populations in different organs and characterized the developmental pathway of mouse and human MAIT cells in the thymus using single-cell RNA sequencing and phenotypic and metabolic analyses. We showed that the predominant mouse subset, which produced IL-17 (MAIT17), and the subset that produced IFN-γ (MAIT1) had not only greatly different transcriptomes but also different metabolic states. MAIT17 cells in different organs exhibited increased lipid uptake, lipid storage, and mitochondrial potential compared with MAIT1 cells. All these properties were similar in the thymus and likely acquired there. Human MAIT cells in lung and blood were more homogeneous but still differed between tissues. Human MAIT cells had increased fatty acid uptake and lipid storage in blood and lung, similar to human CD8 T resident memory cells, but unlike mouse MAIT17 cells, they lacked increased mitochondrial potential. Although mouse and human MAIT cell transcriptomes showed similarities for immature cells in the thymus, they diverged more strikingly in the periphery. Analysis of pet store mice demonstrated decreased lung MAIT17 cells in these so-called "dirty" mice, indicative of an environmental influence on MAIT cell subsets and function.
    MeSH term(s) Humans ; Mucosal-Associated Invariant T Cells ; Transcriptome ; CD8-Positive T-Lymphocytes ; Thymus Gland ; Lipids
    Chemical Substances Lipids
    Language English
    Publishing date 2023-11-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.abn8531
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article: Antigen receptor-redirected T cells derived from hematopoietic precursor cells lack expression of the endogenous TCR/CD3 receptor and exhibit specific antitumor capacities.

    Van Caeneghem, Yasmine / De Munter, Stijn / Tieppo, Paola / Goetgeluk, Glenn / Weening, Karin / Verstichel, Greet / Bonte, Sarah / Taghon, Tom / Leclercq, Georges / Kerre, Tessa / Debets, Reno / Vermijlen, David / Abken, Hinrich / Vandekerckhove, Bart

    Oncoimmunology

    2017  Volume 6, Issue 3, Page(s) e1283460

    Abstract: Recent clinical studies indicate that adoptive T-cell therapy and especially chimeric antigen receptor (CAR) T-cell therapy is a very potent and potentially curative treatment for B-lineage hematologic malignancies. Currently, autologous peripheral blood ...

    Abstract Recent clinical studies indicate that adoptive T-cell therapy and especially chimeric antigen receptor (CAR) T-cell therapy is a very potent and potentially curative treatment for B-lineage hematologic malignancies. Currently, autologous peripheral blood T cells are used for adoptive T-cell therapy. Adoptive T cells derived from healthy allogeneic donors may have several advantages; however, the expected occurrence of graft versus host disease (GvHD) as a consequence of the diverse allogeneic T-cell receptor (TCR) repertoire expressed by these cells compromises this approach. Here, we generated T cells from cord blood hematopoietic progenitor cells (HPCs) that were transduced to express an antigen receptor (AR): either a CAR or a TCR with or without built-in CD28 co-stimulatory domains. These AR-transgenic HPCs were culture-expanded on an OP9-DL1 feeder layer and subsequently differentiated to CD5
    Language English
    Publishing date 2017-01-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2645309-5
    ISSN 2162-402X ; 2162-4011
    ISSN (online) 2162-402X
    ISSN 2162-4011
    DOI 10.1080/2162402X.2017.1283460
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Notch induces human T-cell receptor γδ+ thymocytes to differentiate along a parallel, highly proliferative and bipotent CD4 CD8 double-positive pathway.

    Van Coppernolle, S / Vanhee, S / Verstichel, G / Snauwaert, S / van der Spek, A / Velghe, I / Sinnesael, M / Heemskerk, M H / Taghon, T / Leclercq, G / Plum, J / Langerak, A W / Kerre, T / Vandekerckhove, B

    Leukemia

    2012  Volume 26, Issue 1, Page(s) 127–138

    Abstract: In wild-type mice, T-cell receptor (TCR) γδ(+) cells differentiate along a CD4 CD8 double-negative (DN) pathway whereas TCRαβ(+) cells differentiate along the double-positive (DP) pathway. In the human postnatal thymus (PNT), DN, DP and single-positive ( ... ...

    Abstract In wild-type mice, T-cell receptor (TCR) γδ(+) cells differentiate along a CD4 CD8 double-negative (DN) pathway whereas TCRαβ(+) cells differentiate along the double-positive (DP) pathway. In the human postnatal thymus (PNT), DN, DP and single-positive (SP) TCRγδ(+) populations are present. Here, the precursor-progeny relationship of the various PNT TCRγδ(+) populations was studied and the role of the DP TCRγδ(+) population during T-cell differentiation was elucidated. We demonstrate that human TCRγδ(+) cells differentiate along two pathways downstream from an immature CD1(+) DN TCRγδ(+) precursor: a Notch-independent DN pathway generating mature DN and CD8αα SP TCRγδ(+) cells, and a Notch-dependent, highly proliferative DP pathway generating immature CD4 SP and subsequently DP TCRγδ(+) populations. DP TCRγδ(+) cells are actively rearranging the TCRα locus, and differentiate to TCR(-) DP cells, to CD8αβ SP TCRγδ(+) cells and to TCRαβ(+) cells. Finally, we show that the γδ subset of T-cell acute lymphoblastic leukemias (T-ALL) consists mainly of CD4 SP or DP phenotypes carrying significantly more activating Notch mutations than DN T-ALL. The latter suggests that activating Notch mutations in TCRγδ(+) thymocytes induce proliferation and differentiation along the DP pathway in vivo.
    MeSH term(s) Base Sequence ; CD4 Antigens/immunology ; CD8 Antigens/immunology ; Cell Differentiation ; Cell Proliferation ; Coculture Techniques ; DNA Primers ; Humans ; Real-Time Polymerase Chain Reaction ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; Receptors, Notch/physiology ; Thymocytes/cytology ; Thymocytes/immunology
    Chemical Substances CD4 Antigens ; CD8 Antigens ; DNA Primers ; Receptors, Antigen, T-Cell, gamma-delta ; Receptors, Notch
    Language English
    Publishing date 2012-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/leu.2011.324
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: In vitro generation of mature, naive antigen-specific CD8(+) T cells with a single T-cell receptor by agonist selection.

    Snauwaert, S / Verstichel, G / Bonte, S / Goetgeluk, G / Vanhee, S / Van Caeneghem, Y / De Mulder, K / Heirman, C / Stauss, H / Heemskerk, M H M / Taghon, T / Leclercq, G / Plum, J / Langerak, A W / Thielemans, K / Kerre, T / Vandekerckhove, B

    Leukemia

    2013  Volume 28, Issue 4, Page(s) 830–841

    Abstract: Peripheral blood T cells transduced with a tumor-specific T-cell receptor (TCR) face problems of auto-reactivity and lack of efficacy caused by cross-pairing of exogenous and endogenous TCR chains, as well as short term in vivo survival due to activation ...

    Abstract Peripheral blood T cells transduced with a tumor-specific T-cell receptor (TCR) face problems of auto-reactivity and lack of efficacy caused by cross-pairing of exogenous and endogenous TCR chains, as well as short term in vivo survival due to activation and growth factor-induced differentiation. We here studied an alternative strategy for the efficient generation of naive CD8(+) T cells with a single TCR. TCR-transduced human postnatal thymus-derived and adult mobilized blood-derived hematopoietic progenitor cells (HPCs) were differentiated to CD4(+)CD8(+) double-positive T cells using OP9-Delta-like 1 (OP9-DL1) cultures. Addition of the agonist peptide induced double positive cells to cross-present the peptide, leading, in the absence of co-stimulation, to cell cycle arrest and differentiation into mature CD8(+) T cells. Comprehensive phenotypic, molecular and functional analysis revealed the generation of naive and resting CD8(+) T cells through a process similar to thymic positive selection. These mature T cells show a near complete inhibition of endogenous TCRA and TCRB rearrangements and express high levels of the introduced multimer-reactive TCR. Upon activation, specific cytokine production and efficient killing of tumor cells were induced. Using this strategy, large numbers of high-avidity tumor-specific naive T cells can be generated from readily available HPCs without TCR chain cross-pairing.
    MeSH term(s) Adult ; CD8-Positive T-Lymphocytes/immunology ; Cell Differentiation ; Cell Line, Tumor ; Child ; Child, Preschool ; Gene Rearrangement, T-Lymphocyte ; Humans ; Immunotherapy, Adoptive ; Infant ; Infant, Newborn ; Receptors, Antigen, T-Cell/agonists ; Receptors, Antigen, T-Cell/physiology
    Chemical Substances Receptors, Antigen, T-Cell
    Language English
    Publishing date 2013-10-04
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 807030-1
    ISSN 1476-5551 ; 0887-6924
    ISSN (online) 1476-5551
    ISSN 0887-6924
    DOI 10.1038/leu.2013.285
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: The checkpoint for agonist selection precedes conventional selection in human thymus.

    Verstichel, Greet / Vermijlen, David / Martens, Liesbet / Goetgeluk, Glenn / Brouwer, Margreet / Thiault, Nicolas / Van Caeneghem, Yasmine / De Munter, Stijn / Weening, Karin / Bonte, Sarah / Leclercq, Georges / Taghon, Tom / Kerre, Tessa / Saeys, Yvan / Van Dorpe, Jo / Cheroutre, Hilde / Vandekerckhove, Bart

    Science immunology

    2017  Volume 2, Issue 8

    Abstract: The thymus plays a central role in self-tolerance, partly by eliminating precursors with a T cell receptor (TCR) that binds strongly to self-antigens. However, the generation of self-agonist-selected lineages also relies on strong TCR signaling. How ... ...

    Abstract The thymus plays a central role in self-tolerance, partly by eliminating precursors with a T cell receptor (TCR) that binds strongly to self-antigens. However, the generation of self-agonist-selected lineages also relies on strong TCR signaling. How thymocytes discriminate between these opposite outcomes remains elusive. Here, we identified a human agonist-selected PD-1
    Language English
    Publishing date 2017-02-24
    Publishing country United States
    Document type Journal Article
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.aah4232
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: In vitro human embryonic stem cell hematopoiesis mimics MYB-independent yolk sac hematopoiesis.

    Vanhee, Stijn / De Mulder, Katrien / Van Caeneghem, Yasmine / Verstichel, Greet / Van Roy, Nadine / Menten, Björn / Velghe, Imke / Philippé, Jan / De Bleser, Dominique / Lambrecht, Bart N / Taghon, Tom / Leclercq, Georges / Kerre, Tessa / Vandekerckhove, Bart

    Haematologica

    2015  Volume 100, Issue 2, Page(s) 157–166

    Abstract: Although hematopoietic precursor activity can be generated in vitro from human embryonic stem cells, there is no solid evidence for the appearance of multipotent, self-renewing and transplantable hematopoietic stem cells. This could be due to short half- ... ...

    Abstract Although hematopoietic precursor activity can be generated in vitro from human embryonic stem cells, there is no solid evidence for the appearance of multipotent, self-renewing and transplantable hematopoietic stem cells. This could be due to short half-life of hematopoietic stem cells in culture or, alternatively, human embryonic stem cell-initiated hematopoiesis may be hematopoietic stem cell-independent, similar to yolk sac hematopoiesis, generating multipotent progenitors with limited expansion capacity. Since a MYB was reported to be an excellent marker for hematopoietic stem cell-dependent hematopoiesis, we generated a MYB-eGFP reporter human embryonic stem cell line to study formation of hematopoietic progenitor cells in vitro. We found CD34(+) hemogenic endothelial cells rounding up and developing into CD43(+) hematopoietic cells without expression of MYB-eGFP. MYB-eGFP(+) cells appeared relatively late in embryoid body cultures as CD34(+)CD43(+)CD45(-/lo) cells. These MYB-eGFP(+) cells were CD33 positive, proliferated in IL-3 containing media and hematopoietic differentiation was restricted to the granulocytic lineage. In agreement with data obtained on murine Myb(-/-) embryonic stem cells, bright eGFP expression was observed in a subpopulation of cells, during directed myeloid differentiation, which again belonged to the granulocytic lineage. In contrast, CD14(+) macrophage cells were consistently eGFP(-) and were derived from eGFP-precursors only. In summary, no evidence was obtained for in vitro generation of MYB(+) hematopoietic stem cells during embryoid body cultures. The observed MYB expression appeared late in culture and was confined to the granulocytic lineage.
    MeSH term(s) Cell Differentiation ; Cell Lineage ; Cells, Cultured ; Embryoid Bodies ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Endothelium, Vascular/cytology ; Endothelium, Vascular/metabolism ; Flow Cytometry ; Granulocytes/cytology ; Granulocytes/metabolism ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Hematopoiesis/physiology ; Hematopoietic Stem Cells/cytology ; Hematopoietic Stem Cells/metabolism ; Humans ; In Vitro Techniques ; Macrophages/cytology ; Macrophages/metabolism ; Proto-Oncogene Proteins c-myb/genetics ; Proto-Oncogene Proteins c-myb/metabolism ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Transgenes/physiology ; Yolk Sac/cytology ; Yolk Sac/metabolism
    Chemical Substances Proto-Oncogene Proteins c-myb ; RNA, Messenger ; enhanced green fluorescent protein ; Green Fluorescent Proteins (147336-22-9)
    Language English
    Publishing date 2015-02
    Publishing country Italy
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2014.112144
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: RHAMM/HMMR (CD168) is not an ideal target antigen for immunotherapy of acute myeloid leukemia.

    Snauwaert, Sylvia / Vanhee, Stijn / Goetgeluk, Glenn / Verstichel, Greet / Van Caeneghem, Yasmine / Velghe, Imke / Philippé, Jan / Berneman, Zwi N / Plum, Jean / Taghon, Tom / Leclercq, Georges / Thielemans, Kris / Kerre, Tessa / Vandekerckhove, Bart

    Haematologica

    2012  Volume 97, Issue 10, Page(s) 1539–1547

    Abstract: Background: Criteria for good candidate antigens for immunotherapy of acute myeloid leukemia are high expression on leukemic stem cells in the majority of patients with acute myeloid leukemia and low or no expression in vital tissues. It was shown in ... ...

    Abstract Background: Criteria for good candidate antigens for immunotherapy of acute myeloid leukemia are high expression on leukemic stem cells in the majority of patients with acute myeloid leukemia and low or no expression in vital tissues. It was shown in vaccination trials that Receptor for Hyaluronic Acid Mediated Motility (RHAMM/HMMR) generates cellular immune responses in patients with acute myeloid leukemia and that these responses correlate with clinical benefit. It is not clear however whether this response actually targets the leukemic stem cell, especially since it was reported that RHAMM is expressed maximally during the G2/M phase of the cell cycle. In addition, tumor specificity of RHAMM expression remains relatively unexplored.
    Design and methods: Blood, leukapheresis and bone marrow samples were collected from both acute myeloid leukemia patients and healthy controls. RHAMM expression was assessed at protein and mRNA levels on various sorted populations, either fresh or after manipulation.
    Results: High levels of RHAMM were expressed by CD34(+)CD38(+) and CD34(-) acute myeloid leukemia blasts. However, only baseline expression of RHAMM was measured in CD34(+)CD38(-) leukemic stem cells, and was not different from that in CD34(+)CD38(-) hematopoietic stem cells from healthy controls. RHAMM was significantly up-regulated in CD34(+) cells from healthy donors during in vitro expansion and during in vivo engraftment. Finally, we demonstrated an explicit increase in the expression level of RHAMM after in vitro activation of T cells.
    Conclusions: RHAMM does not fulfill the criteria of an ideal target antigen for immunotherapy of acute myeloid leukemia. RHAMM expression in leukemic stem cells does not differ significantly from the expression in hematopoietic stem cells from healthy controls. RHAMM expression in proliferating CD34+ cells of healthy donors and activated T cells further compromises RHAMM-specific T-cell-mediated immunotherapy.
    MeSH term(s) Adult ; Aged ; Animals ; Antigens, CD34/metabolism ; Cell Cycle ; Cell Line, Tumor ; Disease Models, Animal ; Extracellular Matrix Proteins/genetics ; Extracellular Matrix Proteins/immunology ; Extracellular Matrix Proteins/metabolism ; Female ; Gene Expression Regulation, Leukemic ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/immunology ; Hematopoietic Stem Cells/metabolism ; Humans ; Hyaluronan Receptors/genetics ; Hyaluronan Receptors/immunology ; Hyaluronan Receptors/metabolism ; Immunophenotyping ; Immunotherapy ; Leukemia, Myeloid, Acute/immunology ; Leukemia, Myeloid, Acute/therapy ; Lymphocyte Activation/immunology ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Neoplastic Stem Cells/immunology ; Neoplastic Stem Cells/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Young Adult
    Chemical Substances Antigens, CD34 ; Extracellular Matrix Proteins ; Hyaluronan Receptors ; hyaluronan-mediated motility receptor
    Language English
    Publishing date 2012-04-24
    Publishing country Italy
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2012.065581
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  10. Article ; Online: Functionally mature CD4 and CD8 TCRalphabeta cells are generated in OP9-DL1 cultures from human CD34+ hematopoietic cells.

    Van Coppernolle, Stefanie / Verstichel, Greet / Timmermans, Frank / Velghe, Imke / Vermijlen, David / De Smedt, Magda / Leclercq, Georges / Plum, Jean / Taghon, Tom / Vandekerckhove, Bart / Kerre, Tessa

    Journal of immunology (Baltimore, Md. : 1950)

    2009  Volume 183, Issue 8, Page(s) 4859–4870

    Abstract: Human CD34(+) hematopoietic precursor cells cultured on delta-like ligand 1 expressing OP9 (OP9-DL1) stromal cells differentiate to T lineage cells. The nature of the T cells generated in these cultures has not been studied in detail. Since these ... ...

    Abstract Human CD34(+) hematopoietic precursor cells cultured on delta-like ligand 1 expressing OP9 (OP9-DL1) stromal cells differentiate to T lineage cells. The nature of the T cells generated in these cultures has not been studied in detail. Since these cultures do not contain thymic epithelial cells which are the main cell type mediating positive selection in vivo, generation of conventional helper CD4(+) and cytotoxic CD8(+) TCRalphabeta cells is not expected. Phenotypically mature CD27(+)CD1(-) TCRgammadelta as well as TCRalphabeta cells were generated in OP9-DL1 cultures. CD8 and few mature CD4 single-positive TCRalphabeta cells were observed. Mature CD8 single-positive cells consisted of two subpopulations: one expressing mainly CD8alphabeta and one expressing CD8alphaalpha dimers. TCRalphabeta CD8alphaalpha and TCRgammadelta cells both expressed the IL2Rbeta receptor constitutively and proliferated on IL-15, a characteristic of unconventional T cells. CD8alphabeta(+) and CD4(+) TCRalphabeta cells were unresponsive to IL-15, but could be expanded upon TCR stimulation as mature CD8alphabeta(+) and CD4(+) T cells. These T cells had the characteristics of conventional T cells: CD4(+) cells expressed ThPOK, CD40L, and high levels of IL-2 and IL-4; CD8(+) cells expressed Eomes, Runx3, and high levels of granzyme, perforin, and IFN-gamma. Induction of murine or human MHC class I expression on OP9-DL1 cells had no influence on the differentiation of mature CD8(+) cells. Similarly, the presence of dendritic cells was not required for the generation of mature CD4(+) or CD8(+) T cells. These data suggest that positive selection of these cells is induced by interaction between T precursor cells.
    MeSH term(s) CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD40 Ligand/immunology ; CD40 Ligand/metabolism ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cell Differentiation/immunology ; Cell Line ; Coculture Techniques ; DNA-Binding Proteins/immunology ; DNA-Binding Proteins/metabolism ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Hematopoietic Stem Cells/drug effects ; Hematopoietic Stem Cells/immunology ; Hematopoietic Stem Cells/metabolism ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class I/metabolism ; Humans ; Interleukin-15/pharmacology ; Interleukin-2/immunology ; Interleukin-2/metabolism ; Interleukin-4/immunology ; Interleukin-4/metabolism ; Receptors, Antigen, T-Cell, alpha-beta/immunology ; Receptors, Antigen, T-Cell, alpha-beta/metabolism ; Receptors, Interleukin-2/immunology ; Receptors, Interleukin-2/metabolism ; Transcription Factors/immunology ; Transcription Factors/metabolism
    Chemical Substances DNA-Binding Proteins ; Histocompatibility Antigens Class I ; IL2 protein, human ; IL4 protein, human ; Interleukin-15 ; Interleukin-2 ; Receptors, Antigen, T-Cell, alpha-beta ; Receptors, Interleukin-2 ; Transcription Factors ; ZBTB7B protein, human ; CD40 Ligand (147205-72-9) ; Interleukin-4 (207137-56-2)
    Language English
    Publishing date 2009-10-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.0900714
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top