title: An in vivo IL-7 requirement for peripheral Foxp3+ regulatory T cell homeostasis.
abstract: All T cells are dependent on IL-7 for their development and for homeostasis. Foxp3(+) regulatory T cells (Tregs) are unique among T cells in that they are dependent on IL-2. Whether such IL-2 dependency is distinct from or in addition to an IL-7 requirement has been a confounding issue, particularly because of the absence of an adequate experimental system to address this question. In this study, we present a novel in vivo mouse model where IL-2 expression is intact but IL-7 expression was geographically limited to the thymus. Consequently, IL-7 is not available in peripheral tissues. Such mice were generated by introducing a thymocyte-specific IL-7 transgene onto an IL-7 null background. In these mice, T cell development in the thymus, including Foxp3(+) Treg numbers, was completely restored, which correlates with the thymus-specific expression of transgenic IL-7. In peripheral cells, however, IL-7 expression was terminated, which resulted in a general paucity of T cells and a dramatic reduction of Foxp3(+) Treg numbers. Loss of Tregs was further accompanied by a significant reduction in Foxp3(+) expression levels. These data suggest that peripheral IL-7 is not only necessary for Treg survival but also for upregulating Foxp3 expression. Collectively, we assessed the effect of a selective peripheral IL-7 deficiency in the presence of a fully functional thymus, and we document a critical requirement for in vivo IL-7 in T cell maintenance and specifically in Foxp3(+) cell homeostasis.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Kim
authors.forename: Davinna L
authors.initials: DL
authors.lastname: Ligons
authors.forename: Changwan
authors.initials: C
authors.lastname: Hong
authors.forename: Megan A
authors.initials: MA
authors.lastname: Luckey
authors.forename: Hilary R
authors.initials: HR
authors.lastname: Keller
authors.forename: Xuguang
authors.initials: X
authors.lastname: Tai
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lucas
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Gress
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D015851:Interleukin-7