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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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T Cell Types and Functions01:24

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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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Related Experiment Video

Updated: Mar 16, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry
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Temporal increase in thymocyte negative selection parallels enhanced thymic SIRPα+ DC function.

Charles J Kroger1, Bo Wang1, Roland Tisch2,3

  • 1Department of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.

European Journal of Immunology
|August 9, 2016
PubMed
Summary

Negative selection, crucial for preventing autoimmunity like type 1 diabetes, becomes more efficient with age in NOD mice. This improvement correlates with the expansion of functionally superior thymic dendritic cells (DCs).

Keywords:
AutoimmunityCentral toleranceDendritic cellsDiabetesThymus

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Area of Science:

  • Immunology
  • Developmental Biology
  • Autoimmunity

Background:

  • Dysregulation of negative selection contributes to T-cell-mediated autoimmunity.
  • Negative selection is inefficient early in ontogeny and increases with age.
  • The specific events regulating thymic negative selection remain poorly defined.

Purpose of the Study:

  • To examine temporal changes in negative selection efficiency.
  • To investigate alterations in the thymic dendritic cell (DC) compartment during ontogeny.
  • To understand the role of DCs in age-dependent changes in negative selection.

Main Methods:

  • Assessed peptide-induced thymocyte deletion in vivo in newborn versus 4-week-old NOD mice.
  • Analyzed thymocyte sensitivity to apoptosis induction.
  • Characterized thymic DC subset composition (SIRPα+, plasmacytoid, CD8α+) and function (antigen presentation, T-cell stimulation).

Main Results:

  • Peptide-induced thymocyte deletion was reduced in newborn NOD mice compared to 4-week-old mice.
  • Negative selection efficiency increased with age, paralleling enhanced antigen-presenting cell capacity.
  • Thymic DC composition shifted with age, with increased SIRPα+ and plasmacytoid DCs and decreased CD8α+ DCs.
  • Mature SIRPα+ DCs showed enhanced MHC class II antigen presentation and T-cell stimulatory capacity.

Conclusions:

  • Thymic DC-mediated negative selection is limited in newborns and matures with age.
  • The expansion of functionally superior SIRPα+ DCs contributes to increased negative selection efficiency in older mice.
  • These findings provide insights into the developmental regulation of self-tolerance and implications for type 1 diabetes.