In vivo delivery of a microRNA-regulated transgene induces antigen-specific regulatory T cells and promotes immunologic tolerance.

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

Blood

journal_title

Blood

authors

Annoni A,Brown BD,Cantore A,Sergi LS,Naldini L,Roncarolo MG

doi

10.1182/blood-2009-04-214569

subject

Has Abstract

pub_date

2009-12-10 00:00:00

pages

5152-61

issue

25

eissn

0006-4971

issn

1528-0020

pii

blood-2009-04-214569

journal_volume

114

pub_type

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