Synthetic lymphatic tissues

T cells are instrumental in combatting diseases and fostering lasting immunity. Their maturation is a meticulously orchestrated process that takes place within lymph nodes, the central regulatory hubs for immunity. These nodes not only determine the stimulation of specific T cell types but also provide the optimal environment for their activation, ensuring a targeted and potent response. This maturation involves a sequence of events, including initial stimulation, monoclonal expansion, and differentiation. The sequence’s order and duration are vital for cultivating a diverse T cell population and a successful adaptive immune response. As T cells mature, the cellular microenvironment within the lymph nodes continually evolves, leading to changes in the biochemical and biomechanical properties of adjacent cells. Such alterations, like shifts in tissue stiffness or the introduction of various stimulatory ligands, guide T cell maturation and support their differentiation. For example, during T cell expansion, the lymph node environment sees about a 3-fold increase in stiffness, and nearby cells like antigen-presenting cells (APCs) or fibroblastic reticular cells (FRCs) release more stimulatory ligands and cytokines, such as IL-7 and CCL21. However, current in vitro T-cell expansion technologies fall short in replicating this intricate sequence of events. Our project aims to establish ex vivo T-cell expansion pipelines that mirror these in vivo processes, incorporating modules that adjust T-cell microenvironments using synthetic cells. This approach aims to boost the production of high-quality, therapeutic T cells for immunotherapy.