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Related Concept Videos

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...
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...
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...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...

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Measuring Mitochondrial Function of Na&#239;ve and Effector CD8 T Cells
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Functional dichotomy between OX40 and 4-1BB in modulating effector CD8 T cell responses.

Seung-Woo Lee1, Yunji Park, Aihua Song

  • 1Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|September 20, 2006
PubMed
Summary

Tumor Necrosis Factor Receptor (TNFR) family members OX40 and 4-1BB play distinct roles in CD8 T cell responses. OX40 promotes effector function and survival, while 4-1BB initially limits T cell expansion.

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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation

Published on: February 28, 2019

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Biology

Background:

  • Members of the Tumor Necrosis Factor Receptor (TNFR) family are known to provide costimulatory signals to T cells, influencing their function and survival.
  • The specific roles of closely related TNFR family molecules, OX40 and 4-1BB, in CD8 T cell responses require further elucidation.

Purpose of the Study:

  • To compare the distinct roles of OX40 and 4-1BB in the generation of effector CD8 T cells following adenovirus-delivered antigen exposure.
  • To investigate the differential kinetics and functional impact of OX40 and 4-1BB signaling on CD8 T cell responses.

Main Methods:

  • Adenovirus-mediated antigen delivery to mice.
  • Flow cytometry analysis of OX40 and 4-1BB expression on CD8 T cells.
  • Assessment of CD8 T cell proliferation, survival, effector function, and cytokine production in wild-type, OX40-deficient, and 4-1BB-deficient mice.

Main Results:

  • Both OX40 and 4-1BB were induced on responding naive CD8 T cells, with 4-1BB showing faster and more sustained kinetics.
  • OX40-deficient CD8 T cells exhibited impaired accumulation and survival in late-phase primary responses.
  • 4-1BB-deficient CD8 T cells showed hyperresponsiveness and enhanced maturation, while OX40-deficient cells displayed defects in effector markers, cytokine synthesis, and cytotoxicity.

Conclusions:

  • OX40 and 4-1BB exhibit a functional dichotomy in modulating effector CD8 T cell responses.
  • OX40 positively regulates effector function and late-phase accumulation/survival of CD8 T cells.
  • 4-1BB appears to initially act as a negative regulator, limiting the magnitude of primary CD8 T cell responses.