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Related Concept Videos

Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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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.
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...
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T Cell Activation and Clonal Selection01:22

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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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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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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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Special Features of Adaptive Immunity01:20

Special Features of Adaptive Immunity

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The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
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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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ICOS limits memory-like properties and function of exhausted PD-1 + CD8 T cells.

Etienne Humblin, Isabel Korpas, Nataliya Prokhnevska

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    Inducible Costimulator (ICOS) limits CD8 T cell responses during chronic antigen exposure. Inhibiting ICOS enhances anti-tumor immunity and improves T cell function, offering new avenues for cancer immunotherapy.

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    Area of Science:

    • Immunology
    • Cancer Biology
    • T cell exhaustion

    Background:

    • PD-1+ CD8 T cells are crucial for anti-tumor immunity but can become exhausted during persistent antigen stimulation.
    • Progenitor exhausted PD-1+ TCF-1+ CD8 T cells (Tpex) maintain exhausted T cell populations and are a target for cancer immunotherapies.
    • The role of Inducible Costimulator (ICOS) in PD-1+ CD8 T cell responses during chronic antigen exposure remains unclear.

    Purpose of the Study:

    • To investigate the function of ICOS in regulating PD-1+ CD8 T cell responses during chronic antigen stimulation.
    • To determine the impact of ICOS signaling on Tpex differentiation and the quality of virus-specific and tumor-specific CD8 T cells.
    • To evaluate the therapeutic potential of ICOS blockade in chronic infection and cancer models.

    Main Methods:

    • Utilized ICOS-deficient mouse models during chronic viral infection.
    • Administered ICOS-Ligand blockade in established chronic infection and hepatocellular carcinoma mouse models.
    • Analyzed CD8 T cell populations, cytokine production, and tumor growth dynamics.

    Main Results:

    • ICOS deficiency enhanced the number and quality of virus-specific CD8 T cells, promoting effector-like Tex accumulation via increased survival.
    • Loss of ICOS signaling potentiated FoxO1 activity and conferred memory-like features to Tpex.
    • ICOS-Ligand blockade in vivo led to effector-like Tex expansion, reduced viral load, improved anti-tumor CD8 T cell cytokine production, and delayed tumor growth.

    Conclusions:

    • ICOS signaling actively limits CD8 T cell responses during chronic antigen exposure.
    • Inhibition of ICOS can enhance anti-tumor immunity by promoting the generation of functional effector-like T cells.
    • Targeting ICOS represents a promising strategy for improving cancer immunotherapies.