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Related Concept Videos

Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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...
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
T Cell Types and Functions01:24

T Cell Types and Functions

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.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

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Updated: May 19, 2026

Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses
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Published on: May 6, 2019

TNF-induced target cell killing by CTL activated through cross-presentation.

Dirk Wohlleber1, Hamid Kashkar, Katja Gärtner

  • 1Institutes of Molecular Medicine and Experimental Immunology, Universität Bonn, 53105 Bonn, Germany.

Cell Reports
|September 4, 2012
PubMed
Summary

Viruses evade cytotoxic T cell (CTL) immunity, but cross-presentation allows non-infected cells to activate CTLs. These CTLs release tumor necrosis factor (TNF) to kill virus-infected cells, enhancing immune surveillance.

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Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Viruses employ immune escape mechanisms, such as downregulating MHC class I antigen presentation, to evade cytotoxic T cell (CTL) responses.
  • Cross-priming circumvents some viral immune evasion by enabling antigen presentation on non-infected cells, but its efficacy against functionally immune-evading infected cells is limited.

Purpose of the Study:

  • To investigate the mechanisms by which CTLs overcome viral immune escape, particularly in the context of adenovirus infection in hepatocytes.
  • To elucidate the role of cross-presentation and noncanonical CTL effector functions in antiviral immunity.

Main Methods:

  • Utilized adenovirus-infected hepatocytes and liver sinusoidal endothelial cells in an in vitro model.
  • Analyzed the activation of cross-primed effector CTLs and their cytotoxic mechanisms.
  • Investigated the involvement of tumor necrosis factor (TNF) signaling and caspase activation in target cell killing.

Main Results:

  • Cross-presentation of antigens from infected hepatocytes by liver sinusoidal endothelial cells activated cross-primed CTLs.
  • Activated CTLs released TNF, inducing caspase activation and death in virus-infected hepatocytes.
  • TNF receptor signaling specifically eliminated infected hepatocytes with compromised anti-apoptotic defenses.

Conclusions:

  • CTL immune surveillance against viral infections involves two distinct, MHC-restricted effector functions: direct antigen recognition and noncanonical TNF-mediated killing via cross-presentation.
  • Cross-presentation coupled with TNF release provides a crucial mechanism for eliminating infected cells that have developed functional immune escape strategies.