ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Cellular and molecular requirements for the selection of in vitro-generated CD8 T cells reveal a role for Notch.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- A distinct TCRiScience · 2026Article
- T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025Review
- Lymphoid cell development from fetal hematopoietic progenitors and human pluripotent stem cells.Immunological reviews · 2023Review
- Induction of Human T Cell Development In Vitro with OP9-DL4-7FS Cells Expressing Human Cytokines.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Article
- Development of Auto Antigen-specific Regulatory T Cells for Diabetes Immunotherapy.Immune network · 2016Review
- Stem Cell-Derived Regulatory T Cells for Therapeutic Use in Arthritis.Autoimmune and infectious diseases : open access · 2016Article
- In Vitro T-Cell Generation From Adult, Embryonic, and Induced Pluripotent Stem Cells: Many Roads to One Destination.Stem cells (Dayton, Ohio) · 2015Review
- An organized and functional thymus generated from FOXN1-reprogrammed fibroblasts.Nature cell biology · 2014Article
- In vitro generation of mature, naive antigen-specific CD8(+) T cells with a single T-cell receptor by agonist selection.Leukemia · 2014Article
- Utilizing regulatory T cells against rheumatoid arthritis.Frontiers in oncology · 2014Review
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Differentiation of CD8 single-positive (SP) T cells is predicated by the ability of lymphocyte progenitors to integrate multiple signaling cues provided by the thymic microenvironment. In the thymus and the OP9-DL1 system for T cell development, Notch signals are required for progenitors to commit to the T cell lineage and necessary for their progression to the CD4(+)CD8(+) double-positive (DP) stage of T cell development. However, it remains unclear whether Notch is a prerequisite for the differentiation of DP cells to the CD8 SP stage of development. In this study, we demonstrate that Notch receptor-ligand interactions allow for efficient differentiation and selection of conventional CD8 T cells from bone marrow-derived hematopoietic stem cells. However, bone marrow-derived hematopoietic stem cells isolated from Itk(-/-)Rlk(-/-) mice gave rise to T cells with decreased IFN-γ production, but gained the ability to produce IL-17. We further reveal that positive and negative selection in vitro are constrained by peptide-MHC class I expressed on OP9 cells. Finally, using an MHC class I-restricted TCR-transgenic model, we show that the commitment of DP precursors to the CD8 T cell lineage is dependent on Notch signaling. Our findings further establish the requirement for Notch receptor-ligand interactions throughout T cell differentiation, including the final step of CD8 SP selection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.