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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...
Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

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...
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.
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Immunological Memory01:23

Immunological Memory

Immunological memory, a pivotal pillar of the adaptive immune system, is responsible for the body's ability to remember and respond more swiftly and effectively to previously encountered pathogens. This remarkable feature is what makes vaccines so effective in preventing diseases.
What is Immunological Memory?
Immunological memory is an integral function of the immune system that allows it to recognize and react more rapidly and effectively to pathogens previously encountered. This feature is...
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...
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview

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Generation of Induced Regulatory T Cells from Primary Human Na&iuml;ve and Memory T Cells
14:23

Generation of Induced Regulatory T Cells from Primary Human Naïve and Memory T Cells

Published on: April 16, 2012

Memory Th1/Th2 cell generation controlled by Schnurri-2.

Toshinori Nakayama1, Motoko Y Kimura

  • 1Department of Immunology, Graduate School of Medicine, Chiba University, Japan. tnakayama@faculty.chiba-u.jp

Advances in Experimental Medicine and Biology
|August 28, 2010
PubMed
Summary

Schnurri-2 (Shn-2) protein negatively regulates T-helper 2 cell differentiation and allergic inflammation by repressing NF-kappaB. Shn-2 is crucial for effector T-cell survival and the generation of memory T cells.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Schnurri (Shn) proteins are zinc-finger proteins involved in cell growth and signal transduction.
  • Vertebrates possess three Shn orthologues: Shn-1, Shn-2, and Shn-3.
  • Shn-2 plays a role in T-cell differentiation and immune responses.

Purpose of the Study:

  • To investigate the role of Shn-2 in T-helper 2 (Th2) cell differentiation and allergic airway inflammation.
  • To elucidate the mechanism by which Shn-2 regulates T-cell responses, particularly involving NF-kappaB signaling.
  • To determine the impact of Shn-2 deficiency on the generation of memory T cells.

Main Methods:

  • Utilized Shn-2-deficient mice to study T-cell activation and differentiation.
  • Assessed NF-kappaB activation and its downstream targets in CD4 T cells.
  • Analyzed Th2 cell differentiation, allergic airway inflammation, and memory T-cell generation in vivo and in vitro.
  • Investigated protein-protein interactions between Shn-2 and NF-kappaB components.

Main Results:

  • Shn-2 deficiency led to upregulated NF-kappaB activation in CD4 T cells and enhanced Th2 cell differentiation, partly via GATA3.
  • Shn-2 competes with p50 NF-kappaB, inhibiting NF-kappaB-driven promoter activity.
  • Shn-2-deficient mice exhibited exacerbated Th2-driven allergic airway inflammation.
  • Impaired generation of memory Th1/Th2 cells was observed in Shn-2-deficient mice, with increased apoptosis and CD69 expression in effector T cells.
  • Shn-2-mediated repression of NF-kappaB is essential for effector T-cell survival and memory T-cell generation.

Conclusions:

  • Shn-2 acts as a negative regulator of Th2 cell differentiation and allergic responses by repressing NF-kappaB.
  • Shn-2 is critical for maintaining effector T-cell survival and facilitating the formation of memory T cells.
  • The findings highlight Shn-2's importance in immune homeostasis and the transition from effector to memory T-cell states.