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Formation of in vivo immunological synapses (IS) between CTLs and virally infected astrocytes leads astrocyte to polarization mediated by the activation of a Rho‐GTPase signaling pathway.
Author(s) -
Lowenstein Pedro R,
Puntel Mariana,
Barrett Robert,
Yang Jieping,
Sanderson Nicholas,
Bondale Niyati,
Assi Hikmat,
Kroeger Kurt M,
Castro Maria G
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.856.12
Subject(s) - astrocyte , microbiology and biotechnology , gtpase , immunological synapse , cdc42 , biology , immune system , small gtpase , t cell , cytotoxic t cell , in vivo , signal transduction , in vitro , t cell receptor , immunology , neuroscience , central nervous system , biochemistry
Immunological synapses (IS) mediate intercellular communication between T cells and APCs. T cell polarization at the Kupfer‐type IS consists of a peripheral supramolecular activation cluster (pSMAC), which is high in LFA‐1, and a central SMAC, high in TCR. Target virally infected astrocytes also polarize towards the immunological synapse in vivo . Astrocyte polarization in response to physical lesions in vitro is mediated through the activation of a signaling pathway mediated by a family of Rho‐GTPases, and coordinated by Cdc42. Here we tested the hypothesis that that stimulation of a Rho‐GTPase cascade underlies astrocyte polarization in response to an immune attack in vitro and in vivo . To do so, we infected brain astrocytes with a novel adenoviral (Ad) vector expressing a dominant negative variant of Cdc42 (Cdc42DN) and Thymidine Kinase (TK), a marker of infected cells, and analyzed their responses to a T cell attack. We show that during an anti‐viral immune response, infected astrocytes contacted by CTLs become polarized through the activation of a Rho‐GTPase signaling pathway. This work was funded by grants from NINDS/NIH.