T cell activation requires mitochondrial translocation to the immunological synapse

摘要

T helper (T_h) cell activation is required for the adaptive immune response. Formation of the immunological synapse (IS) between T_h cells and antigen-presenting cells is essential for T_h cell activation. IS formation induces the polarization and redistribution of many signaling molecules; however, very little is known about organelle redistribution during IS formation in T_h cells. We show that formation of the IS induced cytoskeleton-dependent mitochondrial redistribution to the immediate vicinity of the IS. Using total internal reflection microscopy, we found that upon stimulation, the distance between the IS and mitochondria was decreased to values <200 nm. Consequently, mitochondria close to the IS took up more Ca~(2+) than the ones farther away from the IS. The redistribution of mitochondria to the IS was necessary to maintain Ca~(2+) influx across the plasma membrane and Ca~(2+)-dependent T_h cell activation. Our results suggest that mitochondria are part of the signaling complex at the IS and that their localization close to the IS is required for T_h cell activation.