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Updated: Aug 13, 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

Negative selection of the T-cell repertoire: where and when does it occur?

Harald von Boehmer1, Pawel Kisielow

  • 1Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA 02115, USA. harald_von_boehmer@dfci.harvard.edu

Immunological Reviews
|February 2, 2006
PubMed

Insights

Negative selection in T-cell development is not solely due to developmental arrest or lineage diversion. Evidence shows both early cortical and later medullary thymocytes are deleted via apoptosis in experimental models.

Area of Science:

  • Immunology
  • T-cell biology
  • Developmental immunology

Background:

  • Negative selection is a critical process in T-cell development, eliminating self-reactive T-cells.
  • Artificial models like superantigen and T-cell receptor (TCR) transgenic mice are used to study negative selection.
  • Uncertainty exists regarding the precise stages and mechanisms of negative selection.

Purpose of the Study:

  • To review experimental evidence clarifying the mechanisms and developmental stages of negative selection.
  • To determine if negative selection involves developmental arrest, lineage diversion, or apoptosis.
  • To identify the specific thymocyte populations targeted during negative selection.

Main Methods:

  • Review of experimental data from superantigen and TCR transgenic mouse models.
  • Analysis of T-cell development stages, including CD4+ CD8+ double-positive cortical and single-positive medullary thymocytes.
  • Assessment of T-cell receptor (TCR) expression timing.

Main Results:

  • Developmental arrest and lineage diversion are excluded as the sole mechanisms of negative selection.
  • Both CD4+ CD8+ double-positive cortical thymocytes and semi-mature, single-positive medullary thymocytes are susceptible to deletion.
  • Deletion occurs in models with both premature and timely T-cell receptor (TCR) expression.

Conclusions:

  • Negative selection primarily involves apoptotic cell death rather than developmental arrest or lineage diversion.
  • Negative selection targets thymocytes at multiple developmental stages within the thymus.
  • These findings refine our understanding of T-cell development and self-tolerance induction.

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