Published online 21 August 2006 doi:10.1084/jem.20060420
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 9, 2095-2107
In vivo mature immunological synapses forming SMACs mediate clearance of virally infected astrocytes from the brain
Carlos Barcia1,2,
Clare E. Thomas4,
James F. Curtin1,2,
Gwendalyn D. King1,2,
Kolja Wawrowsky3,
Marianela Candolfi1,2,
Wei-Dong Xiong1,2,
Chunyan Liu1,2,
Kurt Kroeger1,2,
Olivier Boyer5,
Jerzy Kupiec-Weglinski6,
David Klatzmann5,
Maria G. Castro1,2, and
Pedro R. Lowenstein1,2
1 Board of Governors' Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048
2 Department of Medicine, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, and 3 Department of Endocrinology, Cedars-Sinai Medical Center, Los Angeles, CA 90048
4 Molecular Medicine and Gene Therapy Unit, University of Manchester, Manchester M13 9PT, England, UK
5 Laboratoire de Biologie et Therapeutiques des Pathologies Immunitaires, Centre National de la Recherche Scientifique UMR7087, Universite Pierre et Marie Curie, Groupe Hospitalier Pitie-Salpetriere, 75651 Paris Cedex 13, France
6 Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Department of Surgery, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095
CORRESPONDENCE Pedro R. Lowenstein: lowensteinp{at}cshs.org
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.
Abbreviations used: CNS, central nervous system; c-SMAC, central SMAC; ICAM-1, intercellular adhesion molecule 1; LFA-1, leukocyte function-associated antigen 1; c-SMAC, central SMAC; p-SMAC, peripheral SMAC; SMAC, supramolecular activation cluster; TK, thymidine kinase; i.u., infectious units.
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