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. ORCID: https://orcid.org/0000-0002-9302-1761, 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:	06 May 2023 15:27
URI:	https://orca.cardiff.ac.uk/id/eprint/84740

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