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Series GSE66421 Query DataSets for GSE66421
Status Public on Jun 22, 2015
Title Therapeutic antiviral T cells noncytopathically clear persistently infected microglia after conversion into antigen-presenting cells
Organism Mus musculus
Experiment type Expression profiling by array
Summary Several viruses can infect the mammalian nervous system and induce neurological dysfunction. Adoptive immunotherapy (AI) is an approach that involves administration of antiviral T cells and has shown promise in clinical studies for the treatment of peripheral virus infections in humans such as cytomegalovirus, Epstein-Barr virus, and adenovirus, among others. Clearance of neurotropic infections, on the other hand, is particularly challenging because the central nervous system (CNS) is relatively intolerant of immunopathological reactions. Therefore, it is essential to develop and mechanistically understand therapies that noncytopathically eradicate pathogens from the CNS. Here, we used mice persistently infected from birth with lymphocytic choriomeningitis virus (LCMV) to demonstrate that therapeutic antiviral T cells can completely purge the persistently infected brain without causing blood brain barrier breakdown or tissue damage. Mechanistically, this is accomplished through a tailored release of chemoattractants that recruit antiviral T cells, but few pathogenic innate immune cells such as neutrophils and inflammatory monocytes. Upon arrival, T cells enlisted the support of nearly all brain resident myeloid cells (microglia) by converting them into CD11c+ antigen-presenting cells (APCs) – a cell population also found in the brain of a human immunodeficiency virus infected patient. Two-photon imaging studies revealed that antiviral CD8+ and CD4+ T cells interacted directly with CD11c+ microglia and induced STAT1 signaling, but did not initiate programmed cell death. We propose that noncytopathic CNS viral clearance can be achieved by therapeutic antiviral T cells reliant on restricted chemoattractant production and interactions with apoptosis-resistant microglia.
 
Overall design 6 Mouse Microglia-sorted Brain Samples: 3 (-) AI, 3 (+) AI.
 
Contributor(s) Herz J, Johnson KR, McGavern DB
Citation(s) 26122661
Submission date Mar 02, 2015
Last update date Feb 21, 2018
Contact name Kory R Johnson
E-mail(s) johnsonko@ninds.nih.gov
Phone 301-402-1956
Organization name NINDS/NIH
Department DIR IT & Bioinformatics
Lab Bioinformatics Section
Street address 10/3B01, 9000 Rockville Pike
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (1)
GPL16570 [MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version]
Samples (6)
GSM1622288 Negative_AI_1
GSM1622289 Negative_AI_2
GSM1622290 Negative_AI_3
Relations
BioProject PRJNA276890

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE66421_RAW.tar 56.5 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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