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

ABSTRACT

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.