Document Detail


Transcutaneous Gene Gun Delivery of hNC16A Induces BPAG2-Specific Tolerance.
MedLine Citation:
PMID:  22377765     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Immune recognition and rejection of tissues expressing transfected genes is a major complication of gene replacement therapy for inherited genetic disorders. Owing to the high immunogenicity of human bullous pemphigoid antigen 2 (hBPAG2), the induction and maintenance of tolerance to this neo-antigen is essential to deliver the gene product to patients with epidermolysis bullosa junctionalis. In a skin grafting mouse model, we used gene gun transfection with a construct encoding hNC16A, the immunodominant domain of hBPAG2, to induce antigen-specific immune tolerance. Eighty percent of wild-type mice transfected with hNC16A showed long-term survival of skin grafts expressing hBPAG2. Tolerance was stable and transferable by T cells but not by B cells of tolerant mice to naive hosts. A dense Foxp3(+) regulatory T-cell (T(reg)) infiltrate was noticed in grafts of tolerant mice and depletion of these cells resulted in a loss of tolerance. Taken together, we show that long-lasting hBPAG2-specific tolerance was induced with gene gun delivery of hNC16A through a T(reg)-dependent mechanism. This is of relevance to patients undergoing gene therapy and has broader implications for the treatment of antigen-specific autoimmune diseases.Journal of Investigative Dermatology advance online publication, 1 March 2012; doi:10.1038/jid.2012.19.
Authors:
Monika Ettinger; Doris Peckl-Schmid; Christina Gruber; Martin Laimer; Josef Thalhamer; Helmut Hintner; Iris K Gratz; Johann W Bauer
Related Documents :
22614725 - On the relevance of glycolysis process on brain gliomas.
1552905 - Clustering of genes involved in nitrate assimilation in the cyanobacterium synechococcus.
22917215 - Optochemogenetics (ocg) allows more precise control of genetic engineering in mice with...
22649415 - Construction of an in vivo system for functional analysis of the genes involved in sex ...
3021995 - The promoter for the late gene encoding vp5 of herpes simplex virus type 1 is recognize...
20011605 - Gene structure induced epigenetic modifications of pericarp color1 alleles of maize res...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-01
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  -     ISSN:  1523-1747     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Division of Molecular Dermatology and EB House Austria, Department of Dermatology, Paracelsus Medical University, Salzburg, Austria.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  CD70-CD27 Interaction Augments CD8+ T-Cell Activation by Human Epidermal Langerhans Cells.
Next Document:  MDM2 Inhibitor Nutlin-3a Induces Apoptosis and Senescence in Cutaneous T-Cell Lymphoma: Role of p53.