title: CD1d expression on and regulation of murine hematopoietic stem and progenitor cells.
abstract: In the present study, surface CD1d, which is involved in immune cell interactions, was assessed for effects on hematopoiesis. Mouse BM hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) express CD1d. The numbers and cycling status of HPCs in the BM and spleen of different strains of cd1d(-/-) mice were enhanced significantly, suggesting that CD1d is a negative regulator of HPCs. In support of this, CD1d was required for the SCF and Flt3 ligand synergistic enhancement of CSF induction of HPC colony formation and for HPC response to myelosuppressive chemokines. Colony formation by immature subsets of HPCs was greatly enhanced when normal, but not cd1d(-/-), BM cells were pretreated with CD1d Abs in vitro. These effects required the full CD1d cytoplasmic tail. In contrast, long-term, but not short-term, repopulating HSC engraftment was impaired significantly, an effect that was minimally influenced by the presence of a truncated CD1d cytoplasmic tail. Pretreatment of normal BM cells with CD1d Abs greatly enhanced their engraftment of HSCs. The results of the present study implicate CD1d in a previously unrecognized regulatory role of normal and stressed hematopoiesis.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202-5181, USA. hbroxmey@iupui.edu
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
authors.forename: Kent
authors.initials: K
authors.lastname: Christopherson
authors.forename: Giao
authors.initials: G
authors.lastname: Hangoc
authors.forename: Scott
authors.initials: S
authors.lastname: Cooper
authors.forename: Charlie
authors.initials: C
authors.lastname: Mantel
authors.forename: Gourapura J
authors.initials: GJ
authors.lastname: Renukaradhya
authors.forename: Randy R
authors.initials: RR
authors.lastname: Brutkiewicz
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D055610:Antigens, CD1d / Q000737:chemistry / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D018925:Chemokines / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D005699:Galactosylceramides / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D017434:Protein Structure, Tertiary; D019089:Stem Cell Factor / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000906:Antibodies; D055610:Antigens, CD1d; D018925:Chemokines; D005699:Galactosylceramides; D008565:Membrane Proteins; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein; D007371:Interferon-gamma