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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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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.
Naive T cells that have not yet encountered an antigen express two primary CD...
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Immunodeficiency Diseases01:25

Immunodeficiency Diseases

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Immunodeficiency disorders are conditions in which the immune system's ability to fight infectious disease and cancer is compromised or entirely absent. The immune system comprises a complex network of cells, tissues, and organs that work together to protect the body from potentially harmful invaders. When this system is deficient or not functioning properly, it leaves the body susceptible to infections, diseases, or other complications.
There are three main causes of immunodeficiency...
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Immunological Memory01:23

Immunological Memory

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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...
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B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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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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Cells of the Adaptive Immune Response01:23

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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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T Cell Types and Functions01:24

T Cell Types and Functions

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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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Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
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Chronically Activated T-cells Retain Their Inflammatory Properties in Common Variable Immunodeficiency.

Roos-Marijn Berbers1, M Marlot van der Wal2, Joris M van Montfrans3

  • 1Department of Rheumatology and Clinical Immunology, University Medical Center and Utrecht University, Utrecht, The Netherlands.

Journal of Clinical Immunology
|July 11, 2021
PubMed
Summary

Immune dysregulation in common variable immunodeficiency (CVID) involves T-cell activation and increased tissue migration, not exhaustion. Regulatory T-cells (Tregs) show reduced CTLA-4, suggesting potential dysfunction in CVIDid patients.

Keywords:
AutoimmunityCommon variable immunodeficiency (CVID)Immune dysregulationImmune exhaustionRegulatory T-cellsT-cells

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Area of Science:

  • Immunology
  • Cellular Biology

Background:

  • Common variable immunodeficiency (CVID) is characterized by hypogammaglobulinemia, but immune dysregulation complications suggest broader pathophysiology.
  • While primarily viewed as a B-cell defect, T-cell contributions to CVID-associated immune dysregulation are increasingly recognized.

Purpose of the Study:

  • To investigate T-cell activation, regulation, and migratory capacity in CVID patients with immune dysregulation (CVIDid).
  • To differentiate T-cell profiles between CVIDid patients and those with CVID and infections only (CVIDio).

Main Methods:

  • Flow cytometry was used to analyze T-cell differentiation, activation markers (HLA-DR, Ki67, IFNγ), inhibitory receptors (PD1, LAG3, CTLA4, TIGIT), regulatory T-cells (Tregs), and homing markers.
  • Analysis included 12 healthy controls, 12 CVIDio patients, and 20 CVIDid patients.

Main Results:

  • CVIDid patients exhibited increased CD4+ and CD8+ T-cell activation (HLA-DR+, Ki67+, IFNγ+) and upregulation of inhibitory receptors (PD1, LAG3, CTLA4, TIGIT) compared to CVIDio.
  • Activated T-cells in CVIDid maintained inflammatory potential, with increased capacity for cytokine and cytotoxic molecule production.
  • Regulatory T-cells (Tregs) in CVIDid showed normal frequencies but reduced CTLA-4 expression, particularly on effector Tregs, and T-cells displayed enhanced migratory capacity.

Conclusions:

  • CVIDid is associated with chronic peripheral T-cell activation and increased tissue migratory capacity, rather than functional exhaustion.
  • Reduced CTLA-4 expression on Tregs in CVIDid suggests potential Treg dysfunction.
  • Further research combining T-cell analysis and inflammatory protein profiling may inform future CVIDid treatment strategies.