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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...

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Generation of Orthotopic Pancreatic Tumors and Ex vivo Characterization of Tumor-Infiltrating T Cell Cytotoxicity
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TLR-9 signaling and TCR stimulation co-regulate CD8(+) T cell-associated PD-1 expression.

Raymond M Wong1, Kent A Smith, Victor L Tam

  • 1MannKind Corporation, 28903 Avenue Paine, Valencia, CA, USA.

Immunology Letters
|September 16, 2009
PubMed
Summary

Therapeutic vaccination strategies can be optimized by modulating Toll-like receptor-9 ligand adjuvant doses. This approach reduces Programmed Death-1 (PD-1) expression on CD8(+) T cells, enhancing immune responses.

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Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice

Published on: June 22, 2016

Area of Science:

  • Immunology
  • Vaccinology
  • T cell biology

Background:

  • Elevated Programmed Death-1 (PD-1) expression on T cells can impair immune responses, posing a challenge for effective therapeutic vaccination.
  • Optimizing vaccine formulations requires understanding how different components influence T cell activation and inhibitory receptor expression.

Purpose of the Study:

  • To investigate the impact of Toll-like receptor (TLR)-9 ligand CpG oligodeoxynucleotide (ODN) adjuvant dosage on Programmed Death-1 (PD-1) expression in epitope-specific CD8(+) T cells.
  • To determine if modulating adjuvant and antigen doses can synergistically regulate PD-1 expression and enhance T cell function.

Main Methods:

  • A direct lymph node-targeted vaccination method was employed, uncoupling peptide (signal 1) and adjuvant (signal 2) delivery.
  • Varied doses of CpG ODN adjuvant were administered with synthetic peptide vaccines.
  • Programmed Death-1 (PD-1) expression and ex vivo function of epitope-specific CD8(+) T cells were assessed.

Main Results:

  • Vaccination without adjuvant led to significantly elevated PD-1 expression on CD8(+) T cells, impairing their function.
  • Increasing doses of CpG ODN adjuvant progressively reduced PD-1 expression and enhanced CD8(+) T cell function.
  • Co-titration of peptide and CpG ODN doses resulted in the lowest PD-1 expression levels.

Conclusions:

  • Toll-like receptor (TLR)-9 ligand adjuvants can be strategically used to elicit CD8(+) T cells with low Programmed Death-1 (PD-1) expression.
  • Fine-tuning both TCR-independent (adjuvant dose) and TCR-dependent (antigen dose) stimuli synergistically regulates PD-1 expression on CD8(+) T cells.
  • These findings offer insights into optimizing therapeutic vaccination and understanding PD-1-mediated T cell homeostasis.