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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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Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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T Cell Types and Functions01:24

T Cell Types and Functions

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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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Renewal of Intestinal Stem Cells01:23

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The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
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Regulation of Hematopoietic Stem Cells01:01

Regulation of Hematopoietic Stem Cells

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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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Related Experiment Video

Updated: Jul 6, 2025

A Three-dimensional Thymic Culture System to Generate Murine Induced Pluripotent Stem Cell-derived Tumor Antigen-specific Thymic Emigrants
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CD4+ T cell immunity is dependent on an intrinsic stem-like program.

Dawei Zou1,2, Zheng Yin3,4, Stephanie G Yi5,6

  • 1Immunobiology & Transplant Science Center, Department of Surgery, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA.

Nature Immunology
|January 3, 2024
PubMed
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Researchers discovered a stem-like program in CD4+ T cells that controls immune responses in transplantation. This program involves TCF1hi effector precursor cells that replenish effector cells, crucial for allograft rejection and potential immunotherapy targets.

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Area of Science:

  • Immunology
  • Transplantation Immunology
  • Cellular Immunology

Background:

  • CD4+ T cells are critical for immune responses, but the molecular mechanisms governing their long-term immunity are not fully understood.
  • Understanding these mechanisms is vital for advancing T cell-based immunotherapies and managing transplant outcomes.

Purpose of the Study:

  • To identify the molecular programs regulating CD4+ T cell immunity in transplantation models.
  • To elucidate the mechanisms behind CD4+ T cell self-renewal and effector differentiation in the context of allograft rejection.

Main Methods:

  • Single-cell transcriptomic analysis of CD4+ T cells in transplantation models.
  • Adoptive transfer experiments to assess T cell function and allograft rejection.
  • Genetic manipulation (deletion) of key transcription factors (IRF4) and enzymes (LDHA) in T cells.

Main Results:

  • Naive CD4+ T cells differentiate into TCF1hi effector precursor (TEP) cells and TCF1-CXCR6+ effector cells.
  • TCF1hi TEP cells possess self-renewal and differentiation potential, continuously supplying effector cells necessary for allograft rejection.
  • IRF4 and LDHA are critical for effector differentiation; their deletion leads to transplant acceptance.

Conclusions:

  • A stem-like program governed by TCF1, IRF4, and LDHA regulates CD4+ T cell self-renewal and effector function in transplantation.
  • Targeting this program offers potential therapeutic strategies for modulating T cell responses in transplantation and immunotherapy.