Volume 8 Supplement 1
HTLV-1 bZIP factor induces systemic inflammations in vivo
© Taguchi et al; licensee BioMed Central Ltd. 2011
Published: 6 June 2011
Human T-cell leukemia virus type 1 (HTLV-1) causes both neoplastic and inflammatory diseases, which include HTLV-1 associated myelopathy/tropic spastic paraparesis and uveitis. Recently, we have reported that transgenic expression of HTLV-1 bZIP factor (HBZ) in CD4+ T cells caused dermatitis and alveolitis in mice. In this study, we investigated the production of cytokines in HBZ transgenic (HBZ-Tg) mice to elucidate the mechanism of its pro-inflammatory phenotype. IFN-γ production in CD4+ T cells was remarkably increased in splenocytes, lungs and PBMCs from HBZ-Tg compared with non-transgenic littermates, whereas there was no difference in levels of IL-4 and IL-17. We also found that production of IFN-γ was remarkably enhanced in CD4+Foxp3- fraction.
Recent studies have reported that CD4+Foxp3+ T cells are not terminally differentiated but have a plasticity to convert to other T cell subsets. Induced regulatory T cells (iTreg) tend to lose Foxp3 expression, and may acquire an effector phenotype accompanied by the production of inflammatory cytokines, such as IFN-γ. We observed that the percentage of naturally occurring Treg cells was lower in HBZ-Tg mice than non-Tg mice, although total number of Treg was increased in HBZ-Tg mice. It is suggested that the enhanced generation of iTreg cells and instability of Foxp3 expression in HBZ-induced iTreg is a possible mechanism for increased number IFN-γ producing cells in HBZ-Tg mice, leading to systemic inflammation.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.