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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
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T Cell factor 1 represses CD8+ effector T cell formation and function.

Machteld M Tiemessen1, Miranda R M Baert1, Lianne Kok1

  • 1Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC/Leiden, the Netherlands.

Journal of Immunology (Baltimore, Md. : 1950)
|October 31, 2014
PubMed
Summary
This summary is machine-generated.

Transcription factor T cell factor 1 (Tcf1) normally suppresses CD8(+) T effector cell formation. Tcf1 deficiency accelerates T cell activation, enhancing anti-viral immunity.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T cell factor 1 (Tcf1) is a Wnt-responsive transcription factor crucial for T cell development and memory formation.
  • The role of Tcf1 in the early stages of CD8(+) T effector cell differentiation remains largely unknown.

Purpose of the Study:

  • To investigate the function of Tcf1 in the generation of CD8(+) T effector cells.
  • To elucidate the molecular mechanisms by which Tcf1 influences T cell effector function.

Main Methods:

  • Analysis of Tcf1 and Wnt signaling levels in naive, memory, and effector CD8(+) T cells.
  • Assessment of Tcf1-deficient CD8(+) T cells for IFN-γ production, T-bet and Blimp1 expression, and demethylation of the IFN-γ enhancer.
  • Evaluation of virus-specific Tcf1(-/-) CD8(+) T cell expansion and function during acute viral infection.
  • Genetic complementation studies using various Tcf1 isoforms.

Main Results:

  • Wnt signaling and Tcf1 expression are high in naive/memory CD8(+) T cells but low in effector CD8(+) T cells.
  • Tcf1-deficient CD8(+) T cells exhibit rapid IFN-γ production, increased T-bet/Blimp1 expression, and enhanced demethylation of the IFN-γ enhancer.
  • Tcf1(-/-) CD8(+) T cells display accelerated expansion, heightened IFN-γ/TNF production, and reduced viral load during acute infection.
  • Tcf1 dosage and protein stability are critical for suppressing IFN-γ production, independent of the β-catenin binding domain.

Conclusions:

  • Tcf1 acts as a repressor of CD8(+) T effector cell formation.
  • This repression occurs in a manner independent of the canonical β-catenin/Wnt pathway.
  • Tcf1 plays a critical role in regulating the balance between T cell effector function and immune memory.