Eintrag weiter verarbeiten
In vivo delivery of a microRNA-regulated transgene induces antigen-specific regulatory T cells and promotes immunologic tolerance
Gespeichert in:
Personen und Körperschaften: | , , , , , |
---|---|
Titel: |
In vivo delivery of a microRNA-regulated transgene induces antigen-specific regulatory T cells and promotes immunologic tolerance |
In: | Blood, 114, 2009, 25, S. 5152-5161 |
veröffentlicht: |
American Society of Hematology
|
Umfang: | 5152-5161 |
ISSN: |
0006-4971 1528-0020 |
DOI: | 10.1182/blood-2009-04-214569 |
Zusammenfassung: | <jats:title>Abstract</jats:title><jats:p>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.</jats:p> |
Format: | E-Article |
Quelle: | American Society of Hematology (CrossRef) |
Sprache: | Englisch |