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Cell-mediated Immune Responses01:40

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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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An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
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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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Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade
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STING negatively regulates allogeneic T-cell responses by constraining antigen-presenting cell function.

Yongxia Wu1, Chih-Hang Anthony Tang2, Corey Mealer3

  • 1Microbiology & Immunology, Medical University of South Carolina, Charleston, SC, USA. wuyyo@musc.edu.

Cellular & Molecular Immunology
|January 27, 2021
PubMed
Summary
This summary is machine-generated.

Stimulator of interferon genes (STING) deficiency in host immune cells worsens graft-versus-host disease (GVHD) after transplantation. STING activation suppresses immune cell activity, offering a potential therapeutic target to control GVHD.

Keywords:
Stimulator of interferon genesT cellsallogeneic hematopoietic cell transplantationantigen-presenting cellsgraft-versus-host diseaseshematopoietic stem-cell transplantation

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Area of Science:

  • Immunology
  • Transplantation Immunology
  • Innate Immunity

Background:

  • Stimulator of interferon genes (STING) signaling is crucial for innate immune responses.
  • STING's role in host cells during allogeneic hematopoietic cell transplantation (allo-HCT) and graft-versus-host disease (GVHD) is not fully understood.
  • Host hematopoietic antigen-presenting cells (APCs) are critical for initiating GVHD.

Purpose of the Study:

  • To investigate the function of STING in host hematopoietic APCs during GVHD.
  • To determine if STING regulates T-cell allogeneic responses after allo-HCT.

Main Methods:

  • Murine models of allo-HCT were used to study STING's role in hematopoietic APCs.
  • Bone marrow chimeras were employed to pinpoint STING's cell-specific effects.
  • Pharmacologic STING agonists were administered to assess therapeutic potential.

Main Results:

  • STING-deficient recipients exhibited more severe GVHD, primarily due to STING's absence in host hematopoietic cells.
  • STING on host CD11c+ cells suppressed allogeneic T-cell responses.
  • STING deficiency increased APC survival, activation, and function, promoting T-cell expansion and migration, thus exacerbating GVHD.
  • STING agonist treatment reduced GVHD mortality.

Conclusions:

  • STING in host hematopoietic APCs plays a critical suppressive role in GVHD pathogenesis.
  • STING regulates T-cell allogeneic responses by modulating APC activity.
  • STING activation represents a promising therapeutic strategy for mitigating GVHD after allo-HCT.