Obligatory role for cooperative signaling by pre-TCR and Notch during thymocyte differentiation.
Open accessAbstract
The first checkpoint during T cell development, known as beta selection, requires the successful rearrangement of the TCR-beta gene locus. Notch signaling has been implicated in various stages during T lymphopoiesis. However, it is unclear whether Notch receptor-ligand interactions are necessary during beta selection. Here, we show that pre-TCR signaling concurrent with Notch receptor and Delta-like-1 ligand interactions are required for the survival, proliferation, and differentiation of mouse CD4(-)CD8(-) thymocytes to the CD4(+)CD8(+) stage. Furthermore, we address the minimal signaling requirements underlying beta selection and show a hierarchical positioning of key proximal signaling molecules. Collectively, our results demonstrate an essential role for Notch receptor-ligand interactions in enabling the autonomous signaling capacity of the pre-TCR complex.
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Numerous signals impact γδ T cell lineage including TCR signal strength, notch signaling, IL-7R signaling, and the presence of DP thymocytes.
“Numerous signals impact on the γδ T cell lineage including, TCR signal strength, notch signaling, IL-7R signaling and the presence of DP thymocytes [6]–[10].”
From The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis (2011) · cites this paper as [7]
The introductory passage in our copy (labeled Abstract; page not provided) reports that Notch1 has been suggested to influence the αβ-versus-γδ T-cell lineage decision. The paper’s own findings concern pre-TCR and Notch signaling during αβ thymocyte differentiation; they do not establish the claimed roles of TCR signal strength, IL-7R signaling, or the presence of DP thymocytes in the γδ lineage. (LLM, conf=0.85)
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- Capone, M., R. D. Hockett, Jr., and A. Zlotnik. 1998. Kinetics of T cell receptor , ␥, and ␦ rearrangements during adult thymic development: T cell receptor rearrangements are present in CD44 ϩ CD25 ϩ pro-T thymocytes. Proc. Natl. Acad. Sci. USA 95:12522.
- Markowitz, D. G., S. P. Goff, and A. Bank. 1988. Safe and efficient ecotropic and amphotropic packaging lines for use in gene transfer experiments. Trans. Assoc. Am. Physicians 101:212.
- Cho, S. K., T. D. Webber, J. R. Carlyle, T. Nakano, S. M. Lewis, and J. C. Zu ´n ˜iga-Pflu ¨cker. 1999. Functional characterization of B lymphocytes generated in vitro from embryonic stem cells. Proc. Natl. Acad. Sci. USA 96:9797.
- Michie, A. M., J. W. Soh, R. G. Hawley, I. B. Weinstein, and J. C. Zu ´n ˜iga- Pflu ¨cker. 2001. Allelic exclusion and differentiation by protein kinase C-mediated signals in immature thymocytes. Proc. Natl. Acad. Sci. USA 98:609.
- Swat, W., Y. Shinkai, H. L. Cheng, L. Davidson, and F. W. Alt. 1996. Activated Ras signals differentiation and expansion of CD4 ϩ 8 ϩ thymocytes. Proc. Natl. Acad. Sci. USA 93:4683.
- Levelt, C. N., P. Mombaerts, A. Iglesias, S. Tonegawa, and K. Eichmann. 1993. Restoration of early thymocyte differentiation in T-cell receptor -chain-deficient mutant mice by transmembrane signaling through CD3⑀. Proc. Natl. Acad. Sci. USA 90:11401.
Cited by
Sorted by citations
Taghon, T., Yui, M. A., Pant, R., Diamond, R. A., & Rothenberg, E. V. (2006) · Immunity · doi:10.1016/j.immuni.2005.11.012 · Cited by 312 · see citing works
Asymmetric cell division during T cell development controls downstream fate
Pham, K., Shimoni, R., Charnley, M., Ludford-Menting, M. J., Hawkins, E. D., Ramsbottom, K., Oliaro, J., Izon, D., Ting, S. B., Reynolds, J., et al. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201502053 · Cited by 39 · see citing works
The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis
Jabeen, R., Chang, H.-C., Goswami, R., Nutt, S. L., & Kaplan, M. H. (2011) · PLOS ONE · doi:10.1371/journal.pone.0022189 · Cited by 10 · see citing works
- Authors
- Ciofani, M., Schmitt, T. M., Ciofani, A., Michie, A. M., Çuburu, N., Aublin, A., Maryanski, J. L., & Zúñiga-Pflücker, J. C.
- Affiliations
- Sunnybrook Health Science Centre (CA)
- University of Glasgow (GB)
- Institut National de Science et Recherche Medicale Unité 503, IFR 128 BioSciences Lyon-Gerland , Lyon ,
- Structure Fédérative de Recherche Biosciences (FR)
- Department of Immunology, University of Toronto, Sunnybrook and Women’s College Health Sciences Centre , Toronto, Ontario ,
- Corresponding author
- Ciofani, Maria
- Ciofani, Amelia
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-05-01
- Volume
- 172
- Issue
- 9
- Pages
- 5230-5239
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2119042271
- Cited by
- 258
- References
- 0
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 11 · 2020: 5 · 2019: 6 · 2018: 9 · 2017: 3 · 2016: 11 · 2015: 15 · 2014: 9 · 2013: 11 · 2012: 18
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- pre-TCR signaling, Notch signaling, beta-selection, thymocyte differentiation, T cell development, CD4+CD8+ thymocytes, ligand-receptor interactions
- MeSH terms
- Animals, Antibodies, Monoclonal, Cell Differentiation, Cell Division, Cell Line, DNA-Binding Proteins, Fetus, Ligands, Membrane Glycoproteins, Membrane Proteins, Protein Precursors, Thymus Gland, Gene Rearrangement, beta-Chain T-Cell Antigen Receptor, Signal Transduction, T-Lymphocyte Subsets, Receptors, Antigen, T-Cell, alpha-beta, Stromal Cells, CD3 Complex, Mice, Knockout, Coculture Techniques, Genes, T-Cell Receptor beta, Intracellular Signaling Peptides and Proteins, Mice, Receptors, Notch
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