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Related Experiment Video

Updated: Jul 4, 2026

A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl

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Granzyme A-expressing Terminal Effector T Cells Dedifferentiate into Long-lived Memory T Cells.

Nu Zhang¹, Chaoyu Ma², Wei Liao³

¹University of Texas Health Science Center at San Antonio.

Research Square

|July 3, 2026

Summary

Memory T cells are crucial for immunity. This study reveals that early memory T cells originate from cells without granzyme A expression, supporting a bifurcation model, while later memory populations are mixed, integrating linear and bifurcated paths.

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In Vitro Differentiation of Mouse Granulocyte-macrophage-colony-stimulating Factor (GM-CSF)-producing T Helper (THGM) Cells

In Vitro Differentiation of Mouse Granulocyte-macrophage-colony-stimulating Factor (GM-CSF)-producing T Helper (T_HGM) Cells

Published on: September 10, 2018

Area of Science:

Immunology
Cellular Biology
T cell differentiation

Background:

Memory T cells are vital for adaptive immunity, vaccines, and T-cell therapies.
The precise differentiation pathways of memory T cells remain incompletely understood.
Contrasting models, linear and bifurcation, exist regarding T cell memory development.

Purpose of the Study:

To investigate the differentiation pathways of CD8+ T cells during immune responses.
To clarify the role of granzyme A expression in T cell memory formation.
To reconcile existing models of T cell differentiation.

Main Methods:

Utilized a granzyme A-fate mapping mouse line.
Employed an acute viral infection model in mice.
Analyzed granzyme A and granzyme B expression patterns in effector and memory T cells.

Main Results:

Granzyme A expression distinguishes terminal effector CD8+ T cells with reduced polyfunctionality from other effector populations.
Early memory T cells predominantly arise from cells lacking granzyme A expression, supporting the bifurcation model.
Terminal effector T cells expressing granzyme A can dedifferentiate into functional long-term memory T cells.
Late-phase memory T cell populations are heterogeneous, comprising cells from both linear and bifurcated differentiation paths.

Conclusions:

The differentiation of memory T cells involves both bifurcation and linear pathways.
Granzyme A expression serves as a marker for terminal effector cells and influences memory T cell development.
A mixed population of memory T cells ensures comprehensive and balanced immune protection.