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Related Experiment Videos

Impaired negative selection in CD28-deficient mice

P J Noel1, M L Alegre, S L Reiner

  • 1Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Illinois 60637, USA.

Cellular Immunology
|September 11, 1998
PubMed
Summary

The CD28 receptor, crucial for peripheral T cell survival, surprisingly plays a role in thymus negative selection. CD28-deficient mice show reduced thymocyte deletion, indicating CD28

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Area of Science:

  • Immunology
  • Cell Biology

Background:

  • T cell development involves selection processes where T cell receptors (TCRs) interact with self-peptides presented by MHC molecules.
  • Positive and negative selection in the thymus dictate T cell fate, determining self-tolerance and immune competence.
  • CD28 is known to enhance peripheral T cell survival and expansion upon TCR activation.

Purpose of the Study:

  • To investigate the role of the CD28 receptor in regulating thymocyte selection, specifically negative selection.
  • To determine if CD28 influences the deletion of potentially autoreactive T cells during thymic development.

Main Methods:

  • Utilized CD28-deficient mice and wildtype littermates for comparative analysis.
  • Assessed thymocyte numbers and negative selection efficiency by stimulating TCR signaling through antigen or antibody crosslinking.

Related Experiment Videos

  • Evaluated thymocyte apoptosis sensitivity to gamma-irradiation and dexamethasone to rule out generalized survival defects.

    • Main Results:

    • CD28-deficient mice exhibited a 50% increase in thymic cellularity compared to wildtype controls.
    • Negative selection of double-positive thymocytes was significantly impaired in CD28-deficient mice.
    • Thymocytes from both CD28-deficient and wildtype mice showed comparable sensitivity to apoptosis induced by external stimuli.

    Conclusions:

    • CD28 signaling is critical for efficient negative selection of thymocytes in the thymus.
    • Contrary to its peripheral function, CD28 actively participates in initiating intracellular signaling pathways that lead to T cell deletion during development.
    • These findings reveal a distinct role for CD28 in central immune tolerance.