In vivo mature immunological synapses forming SMACs mediate clearance of virally infected astrocytes from the brain.
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.
Barcia
Carlos
C
Board of Governors' Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Thomas
Clare E
CE
Curtin
James F
JF
King
Gwendalyn D
GD
Wawrowsky
Kolja
K
Candolfi
Marianela
M
Xiong
Wei-Dong
WD
Liu
Chunyan
C
Kroeger
Kurt
K
Boyer
Olivier
O
Kupiec-Weglinski
Jerzy
J
Klatzmann
David
D
Castro
Maria G
MG
Lowenstein
Pedro R
PR
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
D046912:Multiprotein Complexes; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase