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
Autor: | Toshihiko Ishida, Yoichi Takaue, Osamu Imataki, Yoshinori Ikarashi, H Makiyama, Yuji Heike, Hiro Wakasugi, A Iizuka |
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Rok vydání: | 2008 |
Předmět: |
Interleukin 2
Adult Male Cancer Research Lymphoma CD14 Injections Subcutaneous Immunology Cell Lipopolysaccharide Receptors Receptors Antigen T-Cell chemical and pharmacologic phenomena Galactosylceramides Peripheral blood mononuclear cell Immunotherapy Adoptive Immunophenotyping Antigens CD1 Granulocyte Colony-Stimulating Factor medicine Immunology and Allergy Humans Genetics (clinical) Cells Cultured Cell Proliferation Transplantation biology Cell growth hemic and immune systems Cell Biology Natural killer T cell Molecular biology Immunity Innate Recombinant Proteins Gene Expression Regulation Neoplastic Killer Cells Natural medicine.anatomical_structure Oncology CD1D biology.protein Leukocytes Mononuclear Interleukin-2 Female Tumor Escape medicine.drug |
Zdroj: | Cytotherapy. 10(5) |
ISSN: | 1477-2566 |
Popis: | 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.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).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.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. |
Databáze: | OpenAIRE |
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