In Vivo Mature Immunological Synapses Forming SMACs Mediate Clearance of Virally Infected Astrocytes From the Brain

Authors

Carlos Barcia, Cedars-Sinai Medical Center
Clare Thomas, University of Manchester
James Curtin, Technological University DublinFollow
Gwendalyn King, Cedars-Sinai Medical Center
Kolja Wawrowsky, Cedars-Sinai Medical Center
Marianela Candolfi, Cedars-Sinai Medical Center
Weidong Xiong, Cedars-Sinai Medical Center
Chunyan Liu, Cedars-Sinai Medical Center
Kurt Kroeger, Cedars-Sinai Medical Center
Olivier Boyer, Universite Pierre et Marie Curie (Paris VI)
Jerzy Kupiec-Weglinski, University of California - Los Angeles
David Klatzmann, Universite Pierre et Marie Curie (Paris VI)
Maria Castro, Cedars-Sinai Medical Center
Pedro Lowenstein, Cedars-Sinai Medical Center

Document Type

Article

Rights

Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence

Publication Details

The Journal of Experimental Medicine, 2006 Sep 4; 203(9): 2095–2107.

Abstract

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.

DOI

10.1084/jem.20060420

Recommended Citation

Barcia C, Thomas CE, Curtin JF, King GD, Wawrowsky K, Candolfi M, Xiong WD, Liu C, Kroeger K, Boyer O, Kupiec-Weglinski J, Klatzmann D, Castro MG, Lowenstein PR. In vivo mature immunological synapses forming SMACs mediate clearance of virally infected astrocytes from the brain. J Exp Med. 2006 Sep 4;203(9):2095-107. doi:10.1084/jem.20060420

Funder

NIH, Bram and Elaine Goldsmith Chair in Gene Therapeutics, The Linda Tallen and David Paul Kane Annual Fellowship, Board of Governors at Cedars Sinai Medical Center.