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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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Cytotoxic T Cells-mediated Immune Response01:27

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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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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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Generation of Human Chimeric Antigen Receptor Regulatory T Cells
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Conserved Region C Functions To Regulate PD-1 Expression and Subsequent CD8 T Cell Memory.

Alexander P R Bally1, Yan Tang1, Joshua T Lee1

  • 1Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and.

Journal of Immunology (Baltimore, Md. : 1950)
|November 30, 2016
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Deleting Conserved Region C (CR-C) reduces programmed death 1 (PD-1) expression, enhancing CD8 T cell memory formation and anti-tumor immunity. This finding has implications for vaccine development and T cell-based therapies.

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Area of Science:

  • Immunology
  • Molecular Biology
  • T cell biology

Background:

  • Programmed death 1 (PD-1) expression on CD8 T cells drives T cell exhaustion during chronic antigen exposure.
  • PD-1 transiently expressed during acute infections can modulate CD8 T cell memory formation.
  • Conserved region C (CR-C) is a critical cis-regulatory element for PD-1 expression, influenced by NFATc1, FoxO1, and NF-κB pathways.

Purpose of the Study:

  • To investigate the in vivo role of CR-C in regulating PD-1 expression and CD8 T cell function.
  • To determine the impact of CR-C deletion on T cell responses during viral infections and tumor challenges.

Main Methods:

  • Generation of a CR-C knockout mouse model.
  • Assessment of PD-1 expression on CD4 and CD8 T cells following lymphocytic choriomeningitis virus (LCMV) infection (acute and chronic).
  • Evaluation of CD8 T cell memory formation, functionality, and anti-tumor efficacy in response to a melanoma tumor model.

Main Results:

  • CR-C deletion significantly decreased PD-1 expression on CD4 and Ag-specific CD8 T cells during both acute and chronic LCMV infections.
  • CR-C knockout mice effectively cleared LCMV infections, indicating no impairment in pathogen clearance.
  • Following acute LCMV infection, CR-C knockout mice generated a greater number of more functional memory CD8 T cells, which exhibited enhanced anti-tumor activity against melanoma.

Conclusions:

  • CR-C plays a critical role in controlling PD-1 expression in vivo.
  • CR-C influences CD8 T cell differentiation, leading to improved memory formation and anti-tumor immunity.
  • Modulating PD-1 expression via CR-C presents a potential strategy for enhancing vaccine efficacy and clinical immunotherapies.