title: Regulation of hematopoiesis in vitro and in vivo by invariant NKT cells.
abstract: Invariant natural killer T cells (iNKT cells) are a small subset of immunoregulatory T cells highly conserved in humans and mice. On activation by glycolipids presented by the MHC-like molecule CD1d, iNKT cells promptly secrete T helper 1 and 2 (Th1/2) cytokines but also cytokines with hematopoietic potential such as GM-CSF. Here, we show that the myeloid clonogenic potential of human hematopoietic progenitors is increased in the presence of glycolipid-activated, GM-CSF-secreting NKT cells; conversely, short- and long-term progenitor activity is decreased in the absence of NKT cells, implying regulation of hematopoiesis in both the presence and the absence of immune activation. In accordance with these findings, iNKT-cell-deficient mice display impaired hematopoiesis characterized by peripheral-blood cytopenias, reduced marrow cellularity, lower frequency of hematopoietic stem cells (HSCs), and reduced early and late hematopoietic progenitors. We also show that CD1d is expressed on human HSCs. CD1d-expressing HSCs display short- and long-term clonogenic potential and can present the glycolipid alpha-galactosylceramide to iNKT cells. Thus, iNKT cells emerge as the first subset of regulatory T cells that are required for effective hematopoiesis in both steady-state conditions and under conditions of immune activation.
authors.affiliation: Department of Haematology, Imperial College London, Hammersmith Hospital, Du Cane Rd, London W12 0NN, United Kingdom.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kotsianidis
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Silk
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Spanoudakis
authors.forename: Scott
authors.initials: S
authors.lastname: Patterson
authors.forename: Antonio
authors.initials: A
authors.lastname: Almeida
authors.forename: Richard R
authors.initials: RR
authors.lastname: Schmidt
authors.forename: Costas
authors.initials: C
authors.lastname: Tsatalas
authors.forename: George
authors.initials: G
authors.lastname: Bourikas
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.forename: Irene A G
authors.initials: IA
authors.lastname: Roberts
authors.forename: Anastasios
authors.initials: A
authors.lastname: Karadimitris
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006410:Hematopoiesis / Q000187:drug effects / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
chemical_list: D005699:Galactosylceramides; C493154:alpha-galactosylceramide; D016178:Granulocyte-Macrophage Colony-Stimulating Factor