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Immunoengineering

Immunoengineering - Poster Session A

Poster CC13 - Ageing impairs T-cell sensing while conserving motility and deformation capacity

Thursday, October 24, 2024
10:00 AM – 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction: Cell motility is a universal biological mechanism that is fundamental to several key processes including embryonic development, homeostasis, inflammation, wound healing, and regulation of overall health. Shrewd navigation of the local microenvironment is a ubiquitous requirement for appropriate T cell function, which requires acute surveying of nearby physical and chemical signals. Here, we applied a variety of engineered in vitro screening platforms to assess whether ageing, a process associated with a variety of disease states, alters the ability of T cells to migrate, deform, or sense nearby stimuli.

Materials and

Methods: T cells were isolated from the peripheral blood mononuclear cells (PBMCs) of more than 40 de-identified human donors (ages 18 to 93) using density-dependent centrifugation, and subsequently activated and expanded in vitro using a cocktail of CD3/CD28 Dynabeads and recombinant interleukin-2 (IL-2). T cells were plated in hydrogels and/or microfluidic devices of various geometries to profile single-cell motility, deformability, and sensing dynamics using time-lapse microscopy, image segmentation, and computational tracking.

Results, Conclusions, and Discussions: The effect of age on T-cellmotility and deformation was most pronounced when T cells were provided with a chemotactic gradient (SDF-1α) to sense (Fig. 1A). Several bulk metrics of cell motility revealed that the capacity for Tcells to move is conserved in cells from both young and older donors (Fig. 1B), without disrupting their ability to migrate and deform within an engineered pillar forest maze (Fig. 1C).

This work suggests that ageing-related immune dysfunction, particularly of T cells, is tied more closely to chemotactic sensing than to baseline migration or deformation alone. Future work seeks to reveal the biological mechanisms behind these results.

Acknowledgements (Optional):