In vivo mature immunological synapses forming SMACs mediate clearance of virally infected astrocytes from the brain

CARLOS BARCIA; CLIAIRE E THOMAS; JAMES F CURTIN; GWENDALYN D KING; KOLJIA WAWROWSKY; MARIANELA CANDOLFI; WEIDONG XIONG; CHUNYAN LIU; KURT M KROEGER; O BOYER; J KUPIEC-WEGLINSKI; DAVID KLATZMANN; MARIA G CASTRO; MARIA G CASTRO

JOURNAL OF EXPERIMENTAL MEDICINE

ROCKEFELLER UNIV PRESS

Año: 2006 p. 2095 - 2107

0022-1007

The microanatomy of immune clearance of infected brain cells remains poorly understood. Immunological synapses are essential anatomical structures that channel information exchanges between T cell-antigen-presenting cells (APC) during the priming and effector phases of T cells' function, and during natural killer-target cell interactions. The hallmark of immunological synapses established by T cells is the formation of the supramolecular activation clusters (SMACs), in which adhesion molecules such as leukocyte function-associated antigen 1 segregate to the peripheral domain of the immunological synapse (p-SMAC), which surrounds the T cell receptor-rich or central SMAC (c-SMAC). The inability so far to detect SMAC formation in vivo has cast doubts on its functional relevance. Herein, we demonstrate that the in vivo formation of SMAC at immunological synapses between effector CD8+ T cells and target cells precedes and mediates clearance of virally infected brain astrocytes.