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Updated: May 13, 2026

Isolation and Transplantation of Different Aged Murine Thymic Grafts.
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Murine thymic selection quantified using a unique method to capture deleted T cells.

Gretta L Stritesky1, Yan Xing, Jami R Erickson

  • 1Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55414, USA.

Proceedings of the National Academy of Sciences of the United States of America
|March 15, 2013
PubMed
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This summary is machine-generated.

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More T cells undergo negative selection than positive selection in mice, with most deletion occurring in the thymic cortex. This suggests biased T-cell receptor recognition and impacts peripheral T-cell populations.

Area of Science:

  • Immunology
  • T-cell biology
  • Molecular immunology

Background:

  • T-cell development involves positive and negative selection to ensure MHC restriction and self-tolerance.
  • The quantitative balance between positive and negative selection remains poorly defined.
  • Proapoptotic molecules like Bim (bcl2l11) play critical roles in T-cell homeostasis.

Purpose of the Study:

  • To quantify the number of T cells undergoing positive and negative selection in normal mice.
  • To investigate the stage-specific deletion of T cells during thymic selection.
  • To explore the implications of altered selection on peripheral T-cell populations.

Main Methods:

  • Generation of Bim-deficient mice carrying a Nur77(GFP) reporter transgene.
  • Identification and enumeration of T cells undergoing clonal deletion via GFP expression.

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Last Updated: May 13, 2026

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

Published on: May 13, 2015

Examination of Thymic Positive and Negative Selection by Flow Cytometry
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Examination of Thymic Positive and Negative Selection by Flow Cytometry

Published on: October 8, 2012

Isolation, Identification, and Purification of Murine Thymic Epithelial Cells
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  • Analysis of thymocyte populations at double positive (DP) and single positive (SP) stages.
  • Assessment of peripheral T-cell phenotypes in Bim-deficient mice.

    • Main Results:

    • Six times more T cells undergo negative selection than positive selection.
    • Approximately 75% of negative selection occurs at the DP stage in the cortex, with 25% at the SP stage in the medulla.
    • T-cell recognition appears MHC-biased, with more highly reactive thymocytes deleted.
    • Bim(-/-) mice exhibit increased peripheral GFP(hi) cells, indicating antigen experience or anergy.
    • Clonally deleted CD4+ T cells show only slightly stronger TCR signaling than regulatory T cells.

    Conclusions:

    • Negative selection significantly outweighs positive selection during T-cell development.
    • The majority of T-cell deletion occurs early in thymic development (DP stage).
    • T-cell receptor signaling strength is a critical, albeit nuanced, factor in determining thymocyte fate (deletion vs. regulatory T cell development).
    • Altered selection dynamics impact peripheral T-cell populations and self-tolerance maintenance.