title: Insufficient ex vivo expansion of Valpha24(+) natural killer T cells in malignant lymphoma patients related to the suppressed expression of CD1d molecules on CD14(+) cells.
abstract: BACKGROUND
  Valpha24(+) natural killer T (NKT) cell is a human counterpart of mice Valpha14(+) NKT cell that has a regulatory role for innate and acquired potential antitumor activity. The efficient expansion of NKT cells is an obstacle to the clinical application of Valpha24(+) NKT cells for immunotherapy.
  
  
  METHODS
  We used mononuclear cells (MNC) obtained from the peripheral blood (PB) of normal healthy donor (HD) and malignant lymphoma (ML) patients before and after granulocyte colony-stimulating factor (G-CSF) treatment. MNC were cultured for 12 days with alpha-galactosylceramide (100 ng/mL) and interleukin-2 (IL-2; 100 U/mL).
  
  
  RESULTS
  The fold expansion of Valpha24(+) NKT cells was higher in HD than in ML patients (208 versus 0.00), despite comparable numbers of Valpha24(+) NKT cells before culture. G-CSF administration enhanced the predominance of Valpha24(+) NKT cell fold expansion in HD compared with ML patients (1935 versus 1.95). After treatment with G-CSF, the expression of CD1d molecules was up-regulated in CD14(+) cells from HD but not ML patients. The fold expansion of Valpha24(+) NKT cells and CD1d expression on CD14(+) cells was strongly correlated in both HD and ML patients (r(2)=0.84). However, replacement of a patient's CD14(+) cells with HD cells did not increase the efficacy of Valpha24(+) NKT cell expansion.
  
  
  CONCLUSIONS
  G-CSF-mobilized PB from ML patients has inhibitory characteristics for Valpha24(+) NKT cell expansion as a result of both monocytes and Valpha24(+) NKT cells. Multiple procedures would be needed for the expansion of patients' Valpha24(+) NKT cells.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Imataki
authors.forename: Y
authors.initials: Y
authors.lastname: Heike
authors.forename: H
authors.initials: H
authors.lastname: Makiyama
authors.forename: A
authors.initials: A
authors.lastname: Iizuka
authors.forename: Y
authors.initials: Y
authors.lastname: Ikarashi
authors.forename: T
authors.initials: T
authors.lastname: Ishida
authors.forename: H
authors.initials: H
authors.lastname: Wakasugi
authors.forename: Y
authors.initials: Y
authors.lastname: Takaue
mesh_terms: D000328:Adult; D018949:Antigens, CD1 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology / Q000637:transplantation*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008223:Lymphoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology
chemical_list: D018949:Antigens, CD1; C419394:CD1b antigen; D005699:Galactosylceramides; D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; C528689:Valpha24 protein, human; C493154:alpha-galactosylceramide; D016179:Granulocyte Colony-Stimulating Factor