title: In vivo mature immunological synapses forming SMACs mediate clearance of virally infected astrocytes from the brain.
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.
authors.affiliation: Board of Governors' Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Barcia
authors.forename: Clare E
authors.initials: CE
authors.lastname: Thomas
authors.forename: James F
authors.initials: JF
authors.lastname: Curtin
authors.forename: Gwendalyn D
authors.initials: GD
authors.lastname: King
authors.forename: Kolja
authors.initials: K
authors.lastname: Wawrowsky
authors.forename: Marianela
authors.initials: M
authors.lastname: Candolfi
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Xiong
authors.forename: Chunyan
authors.initials: C
authors.lastname: Liu
authors.forename: Kurt
authors.initials: K
authors.lastname: Kroeger
authors.forename: Olivier
authors.initials: O
authors.lastname: Boyer
authors.forename: Jerzy
authors.initials: J
authors.lastname: Kupiec-Weglinski
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: Maria G
authors.initials: MG
authors.lastname: Castro
authors.forename: Pedro R
authors.initials: PR
authors.lastname: Lowenstein
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000821:virology; D001921:Brain / Q000166:cytology / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D005814:Genes, Viral; D007107:Immune System / Q000033:anatomy & histology / Q000502:physiology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008297:Male; D051379:Mice; D046912:Multiprotein Complexes; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism
chemical_list: D046912:Multiprotein Complexes; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase