Abstract:
:We previously showed that incorporating target sequences for the hematopoietic-specific microRNA miR-142 into an antigen-encoding transgene prevents antigen expression in antigen-presenting cells (APCs). To determine whether this approach induces immunologic tolerance, we treated mice with a miR-142-regulated lentiviral vector encoding green fluorescent protein (GFP), and subsequently vaccinated the mice against GFP. In contrast to control mice, no anti-GFP response was observed, indicating that robust tolerance to the transgene-encoded antigen was achieved. Furthermore, injection of the miR-142-regulated vector induced a population of GFP-specific regulatory T cells. Interestingly, an anti-GFP response was observed when microRNA miR-122a was inserted into the vector and antigen expression was detargeted from hepatocytes as well as APCs. This demonstrates that, in the context of lentiviral vector-mediated gene transfer, detargeting antigen expression from professional APCs, coupled with expression in hepatocytes, can induce antigen-specific immunologic tolerance.
journal_name
Bloodjournal_title
Bloodauthors
Annoni A,Brown BD,Cantore A,Sergi LS,Naldini L,Roncarolo MGdoi
10.1182/blood-2009-04-214569subject
Has Abstractpub_date
2009-12-10 00:00:00pages
5152-61issue
25eissn
0006-4971issn
1528-0020pii
blood-2009-04-214569journal_volume
114pub_type
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