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Evidence That γδ versus αβ T Cell Fate Determination Is Initiated Independently of T Cell Receptor Signaling

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Kang, Joonsoo, Volkmann, Ariane, Raulet, David H.·2001·The Journal of Experimental Medicine
DOI 10.1084/jem.193.6.689PMC PMC2193423
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Abstract

Two types of T cells, αβ and γδ, develop in vertebrates. How these two T cell lineages arise from a common thymic T progenitor is poorly understood. Differentiation of αβ lineage T cells requires the surrogate α chain (pTα), which associates with the T cell receptor (TCR) β chain to form the pre-TCR. γδ lineage development does not appear to involve an obligatory surrogate chain, but instead requires productive rearrangement and expression of both TCR γ and δ genes. It has been proposed that the quality of signals transmitted by the pre-TCR and γδ TCR are distinct and that these “instructive” signals determine the lineage fate of an uncommitted progenitor cell. Here we show that the thymic T progenitor cells (CD25+CD44+c-kit+CD3−CD4−CD8− thymocytes, termed pro-T cells) from young adult mice that have yet to express TCRs can be subdivided based on interleukin 7 receptor (IL-7R) expression. These subsets exhibit differential potential to develop into γδ versus αβ lineage (CD4+CD8+ cells) in the thymus. Upon intrathymic injection, IL-7Rneg-lo pro-T cells generated a 13-fold higher ratio of αβ lineage to γδ lineage cells than did IL-7R+ pro-T cells. Much of this difference was due to a fivefold greater potential of IL-7R+ pro-T cells to develop into TCR-γδ T cells. Evidence indicates that this biased developmental potential is not a result of enhanced TCR-γ gene rearrangement/expression in IL-7R+ pro-T cells. These results indicate that the pro-T cells are heterogeneous in developmental potential before TCR gene rearrangement and suggest that in some precursor cells the initial lineage commitment is independent of TCR-mediated signals.

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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 [9]

    The Introduction discusses competing views of how TCR signals affect γδ versus αβ lineage development, and the Discussion states that IL-7R signaling plays a role in γδ cell development. Our copy does not identify Notch signaling or the presence of double-positive (DP) thymocytes as factors affecting the γδ lineage; it describes DP thymocytes chiefly as an αβ-lineage outcome. It also discusses the quality or role of TCR signals rather than establishing an effect of TCR signal strength. (LLM, conf=0.87)

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Authors
Kang, J., Volkmann, A., & Raulet, D. H.
Affiliations
  • University of Massachusetts Chan Medical School (US)
  • University of California, Berkeley (US)
ORCID
Venue
The Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2001-03-12
Volume
193
Issue
6
Pages
689-698
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.193.6.689
PMC
PMC2193423
OpenAlex
W2138147017
Cited by
122
References
1
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 9 · 2012: 7
FWCI
2.27
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
Funders
  • Damon Runyon Cancer Research Foundation
  • National Institutes of Health
  • National Cancer Institute
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 › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords
γδ T cells, alpha beta T cells, T cell lineage commitment, CD127, T cell receptor signaling, pre-T cell receptor, TCR gamma gene rearrangement, thymocyte differentiation
MeSH terms
Animals, Cell Differentiation, Hematopoietic Stem Cells, Mice, Inbred C57BL, Mice, Transgenic, Receptors, Antigen, T-Cell, T-Lymphocytes, Signal Transduction, Receptors, Antigen, T-Cell, gamma-delta, Receptors, Antigen, T-Cell, alpha-beta, Mice, Knockout, Cell Lineage, Receptors, Interleukin-7, Mice

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