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Evidence for contribution of CD4+CD25+ regulatory T cells in maintaining immune tolerance to human factor IX following perinatal adenovirus vector delivery

Nivsarkar, Megha S., Buckley, Suzanne M. K., Parker, Alan L., Perocheau, Dany, McKay, Tristan R., Rahim, Ahad A., Howe, Steven J. and Waddington, Simon N. 2015. Evidence for contribution of CD4+CD25+ regulatory T cells in maintaining immune tolerance to human factor IX following perinatal adenovirus vector delivery. Journal of Immunology Research 2015 , 397879. 10.1155/2015/397879

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Hindawi Publishing Corporation
ISSN: 2314-8861
Date of First Compliant Deposit: 7 December 2018
Date of Acceptance: 12 January 2015
Last Modified: 11 Jun 2019 10:39
URI: http://orca.cf.ac.uk/id/eprint/84740

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