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Hasani-Sadrabadi, M. M.

Publications and source records attributed to Hasani-Sadrabadi, M. M..

2 recordsLinked to original sources

Augmentation of T-cell activation by oscillatory forces and engineered antigen-presenting cells

Activation of T cells by antigen presenting cells allows them to proliferate, produce cytokines, and kill infected or cancerous cells. We and others have shown that T cell receptors receive and in fact require mechanical forces from their own movements and the movements of antigen presenting cells. Emulation of T cell activation in vitro allows for the massive expansion of T cells necessary for clinical applications. In this paper, we studied the impact of augmenting novel artificial antigen presenting cells of various sizes and antigenic signal strength with mechanical, oscillatory movement. We showed that dynamic culture roughly doubles signal strength as compared to conventional, static culture. We demonstrated that tuning the strength of signal to a \"sweet spot\" allows for robust expansion of induced regulatory T cells, which is impeded by approaches that simply maximize activation.

immunology

T-cell activation is modulated by the 3D mechanical microenvironment

T cells recognize mechanical forces through a variety of cellular pathways, including mechanical triggering of the T-cell receptor (TCR) and mechanical triggering of the integrin LFA-1. We show here that T cells can recognize forces arising from the rigidity of the microenvironment. We fabricated 3D hydrogels with mechanical stiffness tuned to 4 kPa and 40 kPa and specially engineered be microporous independent of stiffness. We cultured T cells and antigen presenting cells within the matrices and studied activation by flow cytometry and live imaging. We found there was an augmentation of T-cell activation in the context of mechanically stiffer 3D material as compared to the softer material. In contrast, proliferation, activation markers, and migration were all diminished in T cells cultured in the softer material. These results show that T cells can sense their mechanical environment and amplify responses in the context of mechanical stiffness.

immunology