Lymphotoxin-Mediated Regulation of γδ Cell Differentiation by αß T Cell Progenitors
Abstract
The thymus gives rise to two T cell lineages, αβ and γδ, that are thought to develop independently of one another. Hence, double positive (DP) thymocytes expressing CD4 and CD8 coreceptors are usually viewed simply as progenitors of CD4 + and CD8 + αβ T cells. Instead we report that DP cells regulate the differentiation of early thymocyte progenitors and γδ cells, by a mechanism dependent on the transcription factor RORgt, and the lymphotoxin (LT) β receptor (LTβR). This finding provokes a revised view of the thymus, in which lymphoid tissue induction-type processes coordinate the developmental and functional integration of the two T cell lineages.
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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 [10]
The phenotype of increased γδ T cells in PU.1-deficient mice is likely cell-intrinsic and not due to effects of αβ T cells on γδ T cell development.
“it is likely that the phenotype observed is cell-intrinsic, and not due to the reported effects of αβ T cells on γδ T cell development [10] because deletion of Sfpi1 by CD4-Cre, where Sfpi1 is deleted in all αβ T cells did not effect γδ T cell numbers in spleen or thymus (data not shown).”
From The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis (2011) · cites this paper as [10]
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Six-of-the-best: unique contributions of γδ T cells to immunology
Vantourout, P., & Hayday, A. (2013) · Nature Reviews Immunology · doi:10.1038/nri3384 · Cited by 1,232 · see citing works
Self-citationRibot, J. C., deBarros, A., Pang, D. J., Neves, J. F., Peperzak, V., Roberts, S. J., Girardi, M., Borst, J., Hayday, A. C., Pennington, D. J., et al. (2009) · Nature Immunology · doi:10.1038/ni.1717 · Cited by 628 · see citing works
Self-citationTaghon, 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
Tumor Necrosis Factor Superfamily in Innate Immunity and Inflammation
Šedý, J., Bekiaris, V., & Ware, C. F. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016279 · Cited by 109 · 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
- Silva-Santos, B., Pennington, D. J., & Hayday, A. C.
- Affiliations
- Peter Gorer Department of Immunobiology, Guy's King's St. Thomas' Medical School, King's College, Guy's Hospital, London SE1 9RT, UK.
- Guy's Hospital (GB)
- Corresponding author
- Pennington, Daniel J.
- Hayday, Adrian C.
- Venue
- Science
- Published
- 2005-02-11
- Volume
- 307
- Issue
- 5711
- Pages
- 925-928
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1498420538
- Cited by
- 147
- References
- 0
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 8 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 5 · 2015: 6 · 2014: 9 · 2013: 7 · 2012: 9
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Wellcome Trust (071534)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- lymphotoxin beta receptor, double-positive thymocytes, T cell development, thymus
- MeSH terms
- Animals, Cell Differentiation, Ligands, Lymphocyte Activation, Lymphotoxin-alpha, Membrane Proteins, Mice, Inbred C57BL, Phenotype, Receptors, Thyroid Hormone, Thymus Gland, Transcription Factors, Tumor Necrosis Factor-alpha, Signal Transduction, Up-Regulation, Gene Expression, T-Lymphocyte Subsets, Receptors, Antigen, T-Cell, gamma-delta, Receptors, Antigen, T-Cell, alpha-beta, Receptors, Tumor Necrosis Factor, Receptors, Retinoic Acid, Cell Lineage, Genes, T-Cell Receptor, Reverse Transcriptase Polymerase Chain Reaction, Mice, Lymphotoxin beta Receptor, Tumor Necrosis Factor Ligand Superfamily Member 14, Nuclear Receptor Subfamily 1, Group F, Member 3
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