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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
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T Cell Types and Functions01:24

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When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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Zfp281 and Zfp148 control CD4+ T cell thymic development and TH2 functions.

Laura B Chopp1,2, Xiaoliang Zhu3, Yayi Gao1

  • 1Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Science Immunology
|November 10, 2023
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Summary

Transcription factors Zfp281 and Zfp148 are crucial for initiating CD4+ T cell development and T helper cell type 2 (TH2) cytokine expression. These factors collaborate with Gata3 to regulate T cell differentiation and immune responses.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Developmental Biology

Background:

  • Initiation of CD4+ lineage gene expression in developing thymocytes is not well understood.
  • T helper cell type 2 (TH2) effector cells are critical for adaptive immunity.

Purpose of the Study:

  • To investigate the role of paralog transcription factors Zfp281 and Zfp148 in CD4+ T cell differentiation and TH2 cytokine expression.
  • To elucidate the interaction between Zfp281, Zfp148, and Gata3 in T cell development.

Main Methods:

  • Genetic analyses
  • Single-cell transcriptomics
  • Spatial transcriptomics
  • Chromatin accessibility assays
  • Protein-DNA interaction studies

Main Results:

  • Zfp281 and Zfp148 promote intrathymic CD4+ T cell differentiation and Thpok expression.
  • These factors enhance TH2 cytokine gene expression and chromatin opening in peripheral T cells.
  • Zfp281 interacts with Gata3 and is recruited to Gata3-bound regulatory regions.

Conclusions:

  • Zfp148 and Zfp281 are key regulators of CD4+ T cell development.
  • These transcription factors collaborate with Gata3 to promote TH2 cell responses.
  • Understanding these mechanisms provides insights into adaptive immunity and T cell differentiation.