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Updated: May 25, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry
14:29

Examination of Thymic Positive and Negative Selection by Flow Cytometry

Published on: October 8, 2012

Thymic negative selection is functional in NOD mice.

Michael Mingueneau1, Wenyu Jiang, Markus Feuerer

  • 1Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.

The Journal of Experimental Medicine
|February 15, 2012
PubMed
Summary
This summary is machine-generated.

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Nonobese diabetic (NOD) mice exhibit impaired T cell selection due to genetic variations affecting early T cell lineage decisions, not negative selection processes in the thymus.

Area of Science:

  • Immunology
  • T cell biology
  • Autoimmunity

Background:

  • Pathogenic T cells in diabetes-prone NOD mice are thought to arise from thymic selection failures.
  • Previous studies suggested NOD genetic variation impairs clonal deletion and transcriptional programs.

Purpose of the Study:

  • To investigate the impact of NOD genetic variation on T cell development and selection.
  • To clarify the mechanisms underlying T cell dysfunction in NOD mice.

Main Methods:

  • Analysis of TCR transgenic (tg) models in NOD and B6 mice.
  • Isolation and preselection of thymocytes.
  • Mixed bone marrow chimera experiments.
  • Biochemical analysis of TCR signalosomes and Erk1/2 activation.

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Isolation and Transplantation of Different Aged Murine Thymic Grafts.
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Isolation and Transplantation of Different Aged Murine Thymic Grafts.

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Last Updated: May 25, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry
14:29

Examination of Thymic Positive and Negative Selection by Flow Cytometry

Published on: October 8, 2012

Preparation and Applications of Organotypic Thymic Slice Cultures
10:10

Preparation and Applications of Organotypic Thymic Slice Cultures

Published on: August 6, 2016

Isolation and Transplantation of Different Aged Murine Thymic Grafts.
05:47

Isolation and Transplantation of Different Aged Murine Thymic Grafts.

Published on: May 13, 2015

Main Results:

  • NOD genetic variation does not impair clonal deletion or transcriptional programs.
  • NOD genetic variation influences αβ/γδ-lineage decisions upon early TCR expression at the double-negative (DN) stage.
  • NOD DN thymocytes show impaired Erk1/2 activation downstream of αβ-TCR signalosomes, leading to increased double-positive (DP) numbers and reduced selection efficiency.

Conclusions:

  • NOD genetic variation affects αβ/γδ-lineage fate decisions during early T cell development.
  • The primary defect in NOD mice lies in altered TCR signaling impacting lineage commitment, not in the negative selection process itself.