Evidence for contribution of CD4+ CD25+ regulatory T cells in maintaining immune tolerance to human factor IX following perinatal adenovirus vector delivery.
- Resource Type
- journal article
- Authors
- Nivsarkar, Megha S; Buckley, Suzanne M K; Parker, Alan L; Perocheau, Dany; McKay, Tristan R; Rahim, Ahad A; Howe, Steven J; Waddington, Simon N
- Source
- Journal of Immunology Research. 2015, Vol. 2015, p397879-397879. 1p.
- Subject
- Language
- ISSN
- 2314-8861
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. [ABSTRACT FROM AUTHOR]