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Related Experiment Video

Updated: Apr 24, 2026

Enrich and Expand Rare Antigen-specific T Cells with Magnetic Nanoparticles

Enrich and Expand Rare Antigen-specific T Cells with Magnetic Nanoparticles

Published on: November 17, 2018

Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy.

Bronwen R Burton¹, Graham J Britton¹, Hai Fang²

¹School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK.

Nature Communications

|September 4, 2014

Summary

Dose escalation in antigen-specific immunotherapy safely induces tolerance by creating anergic, IL-10-secreting regulatory CD4(+) T cells. This approach identifies key transcription factors and co-stimulatory molecules as markers for successful immune tolerance induction.

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Trans-vivo Delayed Type Hypersensitivity Assay for Antigen Specific Regulation

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Published on: May 2, 2013

Area of Science:

Immunology
Immunotherapy
T-cell biology

Background:

Antigen-specific immunotherapy aims to restore immune tolerance for treating autoimmunity and allergies.
Effective immunotherapy requires precise modulation of pathogenic CD4(+) T-cell responses.
Optimizing dosing strategies is crucial for successful tolerance induction.

Purpose of the Study:

To investigate the necessity of dose escalation for subcutaneous delivery of high self-antigen doses in immunotherapy.
To characterize the CD4(+) T-cell response to escalating dose immunotherapy.
To identify molecular signatures associated with successful immune tolerance.

Main Methods:

Subcutaneous administration of escalating doses of self-antigens.
Analysis of CD4(+) T-cell transcriptomes at various immunotherapy stages.
Flow cytometry and gene expression analysis to identify regulatory cell markers.

Main Results:

Dose escalation safely induced anergic, interleukin (IL)-10-secreting regulatory CD4(+) T cells.
Transcriptomic analysis revealed suppression of inflammatory effector pathways and cell cycle pathways.
Key transcription factors (c-Maf, NFIL3) and co-stimulatory molecules (LAG-3, TIGIT, PD-1, TIM-3) were identified on regulatory T cells.

Conclusions:

Dose escalation is essential for effective T-cell-directed immunotherapy and tolerance induction.
Identified immunological and transcriptional signatures serve as surrogate markers for successful immunotherapy.
This study provides a mechanistic rationale for dose escalation strategies in immunotherapy.