title: In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche.
abstract: Stem cells reside in a specialized regulatory microenvironment or niche, where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity. The niche may also protect stem cells from environmental insults including cytotoxic chemotherapy and perhaps pathogenic immunity. The testis, hair follicle and placenta are all sites of residence for stem cells and are immune-suppressive environments, called immune-privileged sites, where multiple mechanisms cooperate to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression. We sought to determine if somatic stem-cell niches more broadly are immune-privileged sites by examining the haematopoietic stem/progenitor cell (HSPC) niche in the bone marrow, a site where immune reactivity exists. We observed persistence of HSPCs from allogeneic donor mice (allo-HSPCs) in non-irradiated recipient mice for 30 days without immunosuppression with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T (T(reg)) cells. High-resolution in vivo imaging over time demonstrated marked co-localization of HSPCs with T(reg) cells that accumulated on the endosteal surface in the calvarial and trabecular bone marrow. T(reg) cells seem to participate in creating a localized zone where HSPCs reside and where T(reg) cells are necessary for allo-HSPC persistence. In addition to processes supporting stem-cell function, the niche will provide a relative sanctuary from immune attack.
authors.affiliation: Advanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. jfujisaki@partners.org
authors.forename: Joji
authors.initials: J
authors.lastname: Fujisaki
authors.forename: Juwell
authors.initials: J
authors.lastname: Wu
authors.forename: Alicia L
authors.initials: AL
authors.lastname: Carlson
authors.forename: Lev
authors.initials: L
authors.lastname: Silberstein
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Putheti
authors.forename: Rafael
authors.initials: R
authors.lastname: Larocca
authors.forename: Wenda
authors.initials: W
authors.lastname: Gao
authors.forename: Toshiki I
authors.initials: TI
authors.lastname: Saito
authors.forename: Cristina
authors.initials: C
authors.lastname: Lo Celso
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuyuzaki
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Sato
authors.forename: Daniel
authors.initials: D
authors.lastname: Côté
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
authors.forename: Terry B
authors.initials: TB
authors.lastname: Strom
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
authors.forename: Charles P
authors.initials: CP
authors.lastname: Lin
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006085:Graft Survival / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D021621:Imaging, Three-Dimensional; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055153:Stem Cell Niche / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016753:Interleukin-10