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T Cell Activation and Clonal Selection

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...

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Ex vivo Expansion of Tumor-reactive T Cells by Means of Bryostatin 1/Ionomycin and the Common Gamma Chain Cytokines Formulation

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Improving T Cell Expansion with a Soft Touch.

Lester H Lambert¹, Geraldine K E Goebrecht¹, Sarah E De Leo¹

¹Department of Biomedical Engineering, Columbia University , New York, New York 10027, United States.

|January 27, 2017

Summary

This summary is machine-generated.

Researchers developed soft, mechanically tunable PDMS microbeads to improve T cell expansion for immunotherapy. These novel beads enhance T cell proliferation and maintain cytotoxic function, offering a promising advancement in T cell therapy.

Keywords:

T cell immunotherapy mechanobiology nanoscale rigidity

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Area of Science:

Biotechnology
Immunology
Materials Science

Background:

Conventional protein-coated microbeads are used for T cell expansion in immunotherapy but lack the properties of natural antigen-presenting cells.
The mechanical properties of the cellular microenvironment significantly influence immune cell function.

Purpose of the Study:

To enhance T cell expansion and function for immunotherapy by utilizing mechanically soft elastomer microbeads.
To investigate the effect of bead material properties, specifically rigidity, on T cell responses.

Main Methods:

Polydimethylsiloxane (PDMS) was fabricated into microbeads and functionalized with CD3 and CD28 activating antibodies.
Three different PDMS formulations were tested for their ability to expand CD4+ and CD4+/CD8+ T cell populations.
T cell cytotoxic function was assessed using biomarkers (perforin, LAMP2, IFN-γ) and in vivo killing assays.

Main Results:

PDMS microbeads supported an extended proliferative phase for both CD4+-only and mixed CD4+-CD8+ T cell preparations.
CD8+ T cells expanded on PDMS beads maintained their cytotoxic function.
PDMS beads exhibited nanoscale polymer structures and higher rigidity than bulk material, suggesting T cells respond to these properties.

Conclusions:

Mechanically soft PDMS microbeads offer an improved platform for T cell expansion compared to conventional rigid beads.
The observed T cell response to PDMS bead rigidity highlights the importance of mechanobiology in immunotherapy bead design.
This approach provides novel tools for advancing T cell-based immunotherapies.