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

Carlos Barcia, Clare E. Thomas, James F. Curtin, Gwendalyn D. King, Kolja Wawrowsky, Marianela Candolfi, Wei Dong Xiong, Chunyan Liu, Kurt Kroeger, Olivier Boyer, Jerzy Kupiec-Weglinski, David Klatzmann, Maria G. Castro, Pedro R. Lowenstein

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

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. JEM

Original languageEnglish (US)
Pages (from-to)2095-2107
Number of pages13
JournalJournal of Experimental Medicine
Volume203
Issue number9
DOIs
StatePublished - Sep 4 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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