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Updated: Jul 8, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry

Examination of Thymic Positive and Negative Selection by Flow Cytometry

Published on: October 8, 2012

No requirement for TRAIL in intrathymic negative selection.

Erika Cretney¹, Adam P Uldrich, Finlay W McNab

¹Cancer Immunology Program, Trescowthick Research Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia.

International Immunology

|January 15, 2008

Summary

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) does not play a role in intrathymic negative selection. Studies show normal immune system development in mice lacking TRAIL signaling, indicating its redundancy in this process.

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Area of Science:

Immunology
Cellular Biology

Background:

The role of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway in intrathymic negative selection is debated.
Conflicting studies exist regarding TRAIL's function in negative selection, with some showing a key role and others demonstrating normal selection in TRAIL-deficient mice.

Purpose of the Study:

To resolve discrepancies regarding TRAIL's contribution to intrathymic negative selection.
To investigate the role of TRAIL in antigen-specific negative selection models.

Main Methods:

Utilized a TCR transgenic system for peptide antigen-specific negative selection.
Employed antibody-mediated TCR/CD3 ligation in vitro and in vivo.
Assessed TRAIL and TRAIL receptor (DR5) expression on thymocytes and dendritic cells.

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Last Updated: Jul 8, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry

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Published on: October 8, 2012

Preparation and Applications of Organotypic Thymic Slice Cultures

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Published on: August 6, 2016

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Examined thymocyte deletion in TRAIL-deficient mice.

Main Results:

TRAIL was not found to be essential in acute negative selection models.
Thymic dendritic cells did not constitutively express TRAIL, and DR5 expression was minimal on thymocytes.
In vitro thymocyte deletion proceeded normally in TRAIL-deficient mice.
Aged TRAIL-deficient mice did not exhibit spontaneous autoimmunity.

Conclusions:

Intrathymic negative selection occurs normally in the absence of TRAIL signaling.
TRAIL and FasL do not appear to function cooperatively in negative selection.
The findings suggest TRAIL is not critical for establishing immune tolerance within the thymus.