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Related Experiment Video

Updated: Feb 10, 2026

Isolation and Activation of Murine Lymphocytes

Isolation and Activation of Murine Lymphocytes

Published on: October 30, 2016

Lymphocyte Activation in Health and Disease.

Michael J Berridge¹

¹The Babraham Institute Laboratory of Molecular Signalling, P. O. Box 158, Cambridge CB2 3ES, U.K.

Critical Reviews in Immunology

|May 19, 2018

Summary

T-cell receptor (TCR) and CD28 signaling pathways orchestrate lymphocyte proliferation and apoptosis. CD28 costimulation is crucial for effective TCR scaffolding, preventing unresponsiveness and enabling immune tolerance.

Area of Science:

Immunology
Cell Signaling
Molecular Biology

Background:

Lymphocytes utilize intricate signaling pathways for proliferation and apoptosis.
T-cell activation is initiated by antigen/MHC binding to the T-cell receptor (TCR).
CD28 costimulation is vital for robust T-cell responses.

Purpose of the Study:

To elucidate the role of CD28 in T-cell receptor complex assembly and signaling.
To understand how CD28 costimulation influences T-cell tolerance and unresponsiveness.
To map the signaling pathways involved in T-cell proliferation and apoptosis.

Main Methods:

Analysis of T-cell signaling cascades including IP3/Ca2+, DAG/PKC, ras/MAPK, and PI 3-K pathways.
Investigation of the structural organization of signaling elements within the TCR complex.

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Examination of downstream signaling events activating IL-2 and Fas pathways.

Main Results:

CD28 facilitates the assembly of an effective signaling scaffold within the TCR complex.
Absence of CD28 costimulation leads to a defective scaffold, promoting T-cell unresponsiveness.
TCR and CD28 signaling activate nuclear factors controlling IL-2 and Fas pathway gene expression.

Conclusions:

CD28 costimulation is essential for maintaining T-cell activation and preventing peripheral tolerance.
Dysfunctional CD28 signaling contributes to immune unresponsiveness.
Understanding these pathways offers therapeutic targets for HIV, autoimmune diseases, and graft rejection.