Evidence for Contribution of CD4 CD25 Regulatory T Cells in Maintaining Immune Tolerance to Human Factor IX following Perinatal Adenovirus Vector DeliveryReportar como inadecuado




Evidence for Contribution of CD4 CD25 Regulatory T Cells in Maintaining Immune Tolerance to Human Factor IX following Perinatal Adenovirus Vector Delivery - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Journal of Immunology Research - Volume 2015 2015, Article ID 397879, 6 pages -

Research Article

Gene Transfer Technology Group, University College London, 86-96 Chenies Mews, London WC1E 6HXZ, UK

Institute of Cancer & Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK

Stem Cell Group, Cardiovascular & Cell Sciences Research Institute, St. George’s University of London, Cranmer Terrace, London SW17 0RE, UK

Department of Pharmacology, School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, UK

Molecular and Cellular Immunology, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK

Antiviral Gene Therapy Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Received 26 November 2014; Accepted 12 January 2015

Academic Editor: Nejat K. Egilmez

Copyright © 2015 Megha S. Nivsarkar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.





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Fuente: https://www.hindawi.com/



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