Artificial Biosystem for Modulation of Interactions between Antigen-Presenting Cells and T Cells

Area of Science:

• Immunology
• Biophysics
• Cellular Biology

Background:

• T cell activation involves signals from antigen-presenting cells (APCs) and cellular forces.
• Understanding these biomechanical and biochemical signals is crucial for improving immunotherapy.
• Mature dendritic cells (mDCs) treated with cytochalasin B show reduced T cell proliferation.

Purpose of the Study:

• To investigate the role of biophysical and biochemical signals in T cell activation.
• To mimic T cell-APC interactions using biomimetic polyacrylamide (PA) gels.
• To understand how substrate stiffness affects T cell proliferation and signaling.

Main Methods:

• Developed biomimetic polyacrylamide (PA) gels with stiffness mimicking mature dendritic cells (mDCs).
• Immobilized varying ratios of anti-CD3 (aCD3) and anti-CD28 (aCD28) antibodies onto PA gels.
• Assessed T cell proliferation, IL-2 secretion, and ZAP70 phosphorylation on different stiffness substrates.

Main Results:

• T cell proliferation was triggered by both aCD3 and aCD28 in a stiffness-dependent manner.
• Anti-CD3 (aCD3) antibodies significantly enhanced proliferation and IL-2 secretion compared to aCD28.
• ZAP70 phosphorylation increased on stiffer substrates in an aCD3-dependent manner.

Conclusions:

• The developed biomimetic system effectively distinguishes the impact of biophysical and biochemical signals.
• Substrate stiffness plays a critical role in T cell activation, proliferation, and cytokine secretion.
• This model provides insights into reduced T cell proliferation observed with cytoskeletal disruption.