title: Autologous bone marrow Th cells can support multiple myeloma cell proliferation in vitro and in xenografted mice.
abstract: Multiple myeloma (MM) is a plasma cell malignancy where MM cell growth is supported by the bone marrow (BM) microenvironment with poorly defined cellular and molecular mechanisms. MM cells express CD40, a receptor known to activate autocrine secretion of cytokines and elicit proliferation. Activated T helper (Th) cells express CD40 ligand (CD40L) and BM Th cells are significantly increased in MM patients. We hypothesized that activated BM Th cells could support MM cell growth. We here found that activated autologous BM Th cells supported MM cell growth in a contact- and CD40L-dependent manner in vitro. MM cells had retained the ability to activate Th cells that reciprocated and stimulated MM cell proliferation. Autologous BM Th cells supported MM cell growth in xenografted mice and were found in close contact with MM cells. MM cells secreted chemokines that attracted Th cells, secretion was augmented by CD40-stimulation. Within 14 days of culture of whole BM aspirates in autologous serum, MM cells and Th cells mutually stimulated each other, and MM cells required Th cells for further expansion in vitro and in mice. The results suggest that Th cells may support the expansion of MM cells in patients.
authors.affiliation: Department of Immunology, Centre for Immune Regulation, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Haematology, Oslo University Hospital, Oslo, Norway.
authors.forename: Y
authors.initials: Y
authors.lastname: Fløisand
authors.affiliation: Department of Immunology, Centre for Immune Regulation, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: C V
authors.initials: CV
authors.lastname: Myklebust
authors.affiliation: Department of Immunology, Centre for Immune Regulation, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Haematology, Oslo University Hospital, Oslo, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Bürgler
authors.affiliation: Department of Immunology, Centre for Immune Regulation, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Parente-Ribes
authors.affiliation: Department of Immunology, Centre for Immune Regulation, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|KG Jebsen Centre for Influenza Vaccine Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: P O
authors.initials: PO
authors.lastname: Hofgaard
authors.affiliation: Department of Immunology, Centre for Immune Regulation, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|KG Jebsen Centre for Influenza Vaccine Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: B
authors.initials: B
authors.lastname: Bogen
authors.affiliation: Centre for Molecular Medicine Norway (NCMM), University of Oslo, Oslo, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Taskén
authors.affiliation: Department of Haematology, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: G E
authors.initials: GE
authors.lastname: Tjønnfjord
authors.affiliation: Department of Immunology, Centre for Immune Regulation, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Haematology, Oslo University Hospital, Oslo, Norway.
authors.forename: F
authors.initials: F
authors.lastname: Schjesvold
authors.affiliation: Department of Haematology, Oslo University Hospital, Oslo, Norway.|Department of Medicine, Vestre Viken Trust, Drammen Hospital, Drammen, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Dalgaard
authors.affiliation: Department of Immunology, Centre for Immune Regulation, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Tveita
authors.affiliation: Department of Immunology, Centre for Immune Regulation, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: L A
authors.initials: LA
authors.lastname: Munthe
mesh_terms: D000368:Aged; D000818:Animals; D017951:Antigen Presentation; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D002455:Cell Division; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D006085:Graft Survival / Q000276:immunology; D064593:Heterografts; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000637:transplantation*; D014182:Transplantation, Autologous / Q000009:adverse effects; D019139:Tumor Escape / Q000276:immunology*; D059016:Tumor Microenvironment
chemical_list: D019013:CD40 Antigens; D018925:Chemokines; D016207:Cytokines; D023201:CD40 Ligand