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Dendritic cells are the principal antigen presenting cells that are responsible for acquiring and transporting antigen from the peripheral tissue to the secondary lymphoid tissue. There they present it to T cells which ultimately initiate an antigen specific immune response. In vivo , the migration of dendritic cells (DCs) and T cell activation are intimately linked. However, ex vivo systems that facilitate integrated evaluation of DC chemotaxis and resulting T cell activation by migrated DCs are lacking. In this work, we have developed a microfabricated platform that integrates DC chemotaxis with T cell activation. The basic design of the microdevice includes two layers of PDMS, with the top layer comprising the chemotaxis compartment and the bottom layer containing a T cell compartment. In the chemotaxis compartment, the DCs are subjected to a chemokine gradient, and their migratory response is evaluated. In the T cell compartment, rapid DC-induced activation of T cells is evaluated by measuring the level of calcium in T cells. We demonstrate the efficacy of our approach by evaluating the integrated response of mature DCs, whereby the overall T cell activation response is governed both by the chemotaxis and the T cell activation potential of mature DCs relative to immature DCs. Our system provides a powerful platform for systematically probing various aspects of antigen induced immune responses - DC maturation, migration and T cell activation - in an integrated fashion.

Microdevice integrating innate and adaptive immune responses associated with antigen presentation by dendritic cells