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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.
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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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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

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Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
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T Cell Factor 1 Suppresses CD103+ Lung Tissue-Resident Memory T Cell Development.

Jingxia Wu1, Alaa Madi2, Alessa Mieg2

  • 1T Cell Metabolism Group (D140), German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.

Cell Reports
|April 9, 2020
PubMed
Summary

T cell factor 1 (Tcf1) regulates tissue-resident memory CD8+ T cell formation. Decreased Tcf1 promotes CD103 expression and T cell numbers in lung tissue after infection.

Keywords:
CD103TRMTcf1influenzamemory CD8+ T cells

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Area of Science:

  • Immunology
  • Cellular Biology
  • Infectious Disease

Background:

  • T cell factor 1 (Tcf1) is crucial for central memory CD8+ T cell differentiation and stemness in lymphoid tissues following systemic infections.
  • The role of Tcf1 in the formation of CD103high tissue-resident memory CD8+ T (T_RM) cells in non-lymphoid tissues after mucosal infections is not well understood.

Purpose of the Study:

  • To investigate the function of Tcf1 in the development of lung T_RM cells after mucosal infections.
  • To elucidate the regulatory mechanisms of Tcf1 on CD103 expression and T_RM cell homeostasis.

Main Methods:

  • Analysis of Tcf1 expression during lung T_RM cell formation in vivo.
  • Investigating the impact of transforming growth factor β (TGF-β) signaling abrogation on T_RM precursors.
  • Utilizing T-cell-specific Tcf7 ablation models to assess T_RM cell development and CD103 expression.
  • Chromatin immunoprecipitation assays to determine Tcf1 binding to the Itgae locus.

Main Results:

  • Tcf1 expression progressively decreases during lung T_RM cell formation.
  • Abrogation of TGF-β signaling leads to reduced CD103+ and increased Tcf1+ T_RM precursors.
  • T-cell-specific ablation of Tcf7 enhances CD103 expression and increases T_RM cell numbers post-infection.
  • Tcf1 directly binds to the Itgae locus and partially inhibits TGF-β-induced CD103 expression.

Conclusions:

  • Tcf1 reciprocally regulates memory T cell tissue residency and homeostatic proliferation.
  • Tcf1 exhibits context-dependent roles, acting either immunosupportively or immunosuppressively in CD8+ T cells based on infection type (systemic vs. mucosal).