Evidence for Contribution of CD4+CD25+ Regulatory T Cells in Maintaining Immune Tolerance to Human Factor IX following Perinatal Adenovirus Vector Delivery
Title: | Evidence for Contribution of CD4+CD25+ Regulatory T Cells in Maintaining Immune Tolerance to Human Factor IX following Perinatal Adenovirus Vector Delivery |
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Authors: | Megha S. Nivsarkar, Suzanne M. K. Buckley, Alan L. Parker, Dany Perocheau, Tristan R. McKay, Ahad A. Rahim, Steven J. Howe, Simon N. Waddington |
Source: | Journal of Immunology Research, Vol 2015 (2015) |
Publisher Information: | Hindawi Limited, 2015. |
Publication Year: | 2015 |
Collection: | LCC:Immunologic diseases. Allergy |
Subject Terms: | Immunologic diseases. Allergy, RC581-607 |
More Details: | Following fetal or neonatal gene transfer in mice and other species immune tolerance of the transgenic protein is frequently observed; however the underlying mechanisms remain largely undefined. In this study fetal and neonatal BALB/c mice received adenovirus vector to deliver human factor IX (hFIX) cDNA. The long-term tolerance of hFIX was robust in the face of immune challenge with hFIX protein and adjuvant but was eliminated by simultaneous administration of anti-CD25+ antibody. Naive irradiated BALB/c mice which had received lymphocytes from donors immunised with hFIX developed anti-hFIX antibodies upon immune challenge. Cotransplantation with CD4+CD25+ cells isolated from neonatally tolerized donors decreased the antibody response. In contrast, cotransplantation with CD4+CD25− cells isolated from the same donors increased the antibody response. These data provide evidence that immune tolerance following perinatal gene transfer is maintained by a CD4+CD25+ regulatory population. |
Document Type: | article |
File Description: | electronic resource |
Language: | English |
ISSN: | 2314-8861 2314-7156 |
Relation: | https://doaj.org/toc/2314-8861; https://doaj.org/toc/2314-7156 |
DOI: | 10.1155/2015/397879 |
Access URL: | https://doaj.org/article/ac77022689344402bb0548d5af363f32 |
Accession Number: | edsdoj.77022689344402bb0548d5af363f32 |
Database: | Directory of Open Access Journals |
ISSN: | 23148861 23147156 |
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DOI: | 10.1155/2015/397879 |
Published in: | Journal of Immunology Research |
Language: | English |