Induction of T Cell Development from Hematopoietic Progenitor Cells by Delta-like-1 In Vitro

Schmitt, Thomas M.; Zúñiga‐Pflücker, Juan Carlos

doi:10.1016/s1074-7613(02)00474-0

Cited by 996 publications

(1,125 citation statements)

References 34 publications

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“…The KN6 TCRγ and TCRδ subunits were cloned into pMiY as a fusion protein linked by the 2A Tescovirus linker peptide, as described previously 14 . OP9-DL1, OP9-DL4 and OP9-Ctrl cells were produced and maintained as previously described 59, 60 , and co-cultures were supplemented with 1 ng mL −1 mouse recombinant IL-7 and 5 ng mL −1 human recombinant Flt-3L (Peprotech). Fetal livers (FL) were obtained from timed-pregnant Rag2 −/− female mice on day (d) 14 of gestation.…”

Section: Methodsmentioning

confidence: 99%

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

Zarin

Chen

et al. 2018

Immunol Cell Biol

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γδ T-cells perform a wide range of tissue and disease specific functions that are dependent on the effector cytokines produced by these cells. However, the aggregate signals required for the development of interferon-γ (IFNγ) and interleukin-17 (IL-17) producing γδ T-cells remain unknown. Here, we define the cues involved in the functional programming of γδ T-cells, by examining the roles of T-cell receptor (TCR), Notch, and cytokine-receptor signaling. KN6 γδTCR-transduced Rag2−/− T-cell progenitors were cultured on stromal cells variably expressing TCR and Notch ligands, supplemented with different cytokines. We found that distinct combinations of these signals are required to program IFNγ versus IL-17 producing γδ T cell subsets, with Notch and weak TCR ligands optimally enabling development of γδ17 cells in the presence of IL-1β, IL-21 and IL-23. Notably, these cytokines were also shown to be required for the intrathymic development of γδ17 cells. Together, this work provides a framework of how signals downstream of TCR, Notch and cytokine receptors integrate to program the effector function of IFNγ and IL-17 producing γδ T-cell subsets.

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Section: Methodsmentioning

confidence: 99%

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

Zarin

Chen

et al. 2018

Immunol Cell Biol

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“…Vol. 66,2009 Review Article 1639 poietic progenitors on these stromal Notch-ligand expressing cells [139]. Notch signaling also potentially plays a role in the development of gamma/delta T-cells and natural killer cell development, reviewed in [107,140].…”

Section: T-cell Developmentmentioning

confidence: 99%

The Notch signaling pathway: Transcriptional regulation at Notch target genes

Borggrefe

Oswald

2009

Cell. Mol. Life Sci.

575

499

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. The Notch gene encodes a transmembrane receptor that gave the name to the evolutionary highly conserved Notch signaling cascade. It plays a pivotal role in the regulation of many fundamental cellular processes such as proliferation, stem cell maintenance and differentiation during embryonic and adult development. After specific ligand binding, the intracellular part of the Notch receptor is cleaved off and translocates to the nucleus, where it binds to the transcription factor RBP-J. In the absence of activated Notch, RBP-J represses Notch target genes by recruiting a corepressor complex. Here, we review Notch signaling with a focus on gene regulatory events at Notch target genes. This is of utmost importance to understand Notch signaling since certain RBP-J associated cofactors and particular epigenetic marks determine the specificity of Notch target gene expression in different cell types. We subsequently summarize the current knowledge about Notch target genes and the physiological significance of Notch signaling in development and cancer.

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“…Notch-based culture systems such as the OP9-DL1 (a mouse bone marrow stromal cell line transduced to express DL1) system [51] can be utilized to generate large numbers of early T cell precursors from hematopoietic stem cells [52]. Transfer of these T cell precursors, along with the allograft, to lethally irradiated allogeneic HSCT recipients resulted in increased thymic cellularity and chimerism, as well as enhanced peripheral T and NK cell reconstitution [52].…”

Section: Committed Precursor Cells Generated By Notch-based Culturementioning

confidence: 99%

Enhancing T cell reconstitution after hematopoietic stem cell transplantation: A brief update of the latest trends

Zakrzewski

Goldberg

Smith

et al. 2008

Blood Cells, Molecules, and Diseases

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Hematopoietic stem cell transplantation (HSCT) is associated with a period of immune incompetence that particularly affects the T cell lineage. Strategies to enhance T cell reconstitution could significantly improve the survival of HSCT recipients by decreasing the incidence of fatal infectious complications and by enhancing graft-versus-tumor activity. In recent years, a variety of promising strategies have been established in preclinical models to improve T cell recovery in particular after allogeneic T cell-depleted HSCT, without aggravating graft-versus-host disease while preserving or even improving graft-versus-tumor activity. These therapies include treatment with keratinocyte growth factor (KGF), growth hormone (GH), LHRH agonists, interleukin 7 (IL-7) and interleukin 15 (IL-15). Thanks to the establishment of Notch-based culture systems, adoptive cellular therapies with T lineage-committed precursor cells have become feasible, since early T cell progenitors can now easily be generated in vitro in large quantities and have been proven to be very effective in enhancing T cell reconstitution and anti-tumor activity after allogeneic T cell-depleted HSCT. The translation of most of these strategies into clinical trials is likely and in some cases Phase I/II studies are already underway.

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Induction of T Cell Development from Hematopoietic Progenitor Cells by Delta-like-1 In Vitro

Cited by 996 publications

References 34 publications

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation

The Notch signaling pathway: Transcriptional regulation at Notch target genes

Enhancing T cell reconstitution after hematopoietic stem cell transplantation: A brief update of the latest trends

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