title: Invariant natural killer T cells generated from human adult hematopoietic stem-progenitor cells are poly-functional.
abstract: Invariant natural killer T (iNKT) cells constitute an important subset of T cells that can both directly and indirectly mediate anti-tumor immunity. However, cancer patients have a reduction in both iNKT cell number and function, and these deficits limit the potential clinical application of iNKT cells for cancer therapy. To overcome the problem of limited iNKT cell numbers, we investigated whether iNKT cells can be generated in vitro from bone marrow-derived adult hematopoietic stem-progenitor cells (HSPC). Our data demonstrate that co-culture of HSPC with OP9-DL1 stromal cells, results in a functional CD3(+) T cell population. These T cells can be further differentiated into iNKT cells by secondary culture with CD1d-Ig-based artificial antigen-presenting cells (aAPC). Importantly, these in vitro-generated iNKT cells are functional, as demonstrated by their ability to proliferate and secrete IFN-γ and GM-CSF following stimulation.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, United States.
authors.forename: Wenji
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Regenerative Medicine, School of Pharmaceutical Sciences, Jilin University, Changchun, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, United States.
authors.forename: James E
authors.initials: JE
authors.lastname: East
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, United States.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Kimball
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, United States.
authors.forename: Katherine
authors.initials: K
authors.lastname: Tkaczuk
authors.affiliation: Department of Surgery, University of Maryland School of Medicine, and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, United States.
authors.forename: Susan
authors.initials: S
authors.lastname: Kesmodel
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland School of Medicine, and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, United States.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Strome
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, and the Marlene and Stewart Greenebaum Cancer Center, Baltimore, MD 21201, United States. Electronic address: twebb@som.umaryland.edu.
authors.forename: Tonya J
authors.initials: TJ
authors.lastname: Webb
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology; D055610:Antigens, CD1d / Q000276:immunology; D002454:Cell Differentiation; D018920:Coculture Techniques; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology
chemical_list: D055610:Antigens, CD1d; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: Adoptive immunotherapy; CD1d; NKT cells; Stem cells