title: Flt3 ligand expands CD4+ FoxP3+ regulatory T cells in human subjects.
abstract: CD4(+) CD25(+) FoxP3(+)  naturally occurring regulatory T (Treg) cells play a crucial role in the maintenance of immune tolerance and in preventing autoimmune pathology. Interventions that expand Treg cells are highly desirable, as they may offer novel treatment options in a variety of autoimmune and transplantation settings. Paralleling previous preclinical studies, we demonstrate here that administration of the hematopoietic growth factor Flt3L to human subjects increases the frequency and absolute number of Treg cells, and reduces the ratio of CD8(+)  T cells to Treg cells in the peripheral blood. The increase in Treg cells was due to enhanced Treg-cell proliferation rather than release of Treg cells from the thymus. Further studies revealed that Flt3L-induced proliferation of Treg cells was an indirect effect that occurred via the interaction of Treg cells with the Flt3L-expanded pool of CD1c(+)  myeloid dendritic cells. On the basis of these findings, Flt3L may represent a promising agent for promoting immune tolerance in a variety of clinical settings.
authors.affiliation: Ludwig Institute for Cancer Research, Melbourne Centre for Clinical Sciences, Heidelberg, Victoria, Australia. oliver.klein@ludwig.edu.au
authors.forename: Oliver
authors.initials: O
authors.lastname: Klein
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Ebert
authors.forename: Damien
authors.initials: D
authors.lastname: Zanker
authors.forename: Katherine
authors.initials: K
authors.lastname: Woods
authors.forename: Bee Shin
authors.initials: BS
authors.lastname: Tan
authors.forename: Jitka
authors.initials: J
authors.lastname: Fucikova
authors.forename: Andreas
authors.initials: A
authors.lastname: Behren
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
authors.forename: Eugene
authors.initials: E
authors.lastname: Maraskovsky
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D048708:Cell Growth Processes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D051941:fms-Like Tyrosine Kinase 3 / Q000276:immunology* / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; C084881:flt3 ligand protein; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3