RRC ID 62157
Author Tanaka J, Toubai T, Tsutsumi Y, Miura Y, Kato N, Umehara S, Kahata K, Mori A, Toyoshima N, Ota S, Kobayashi T, Kobayashi M, Kasai M, Asaka M, Imamura M.
Title Cytolytic activity and regulatory functions of inhibitory NK cell receptor-expressing T cells expanded from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells.
Journal Blood
Abstract Inhibitory natural killer cell receptor (NKR)-expressing cells may induce a graft-versus-leukemia/tumor (GVL/T) effect against leukemic cells and tumor cells that have mismatched or decreased expression of HLA class I molecules and may not cause graft-versus-host disease (GVHD) against host cells that have normal expression of HLA class I molecules. In our study, we were able to expand inhibitory NKR (CD94/NKG2A)-expressing CD8+ T cells from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood mononuclear cells (G-PBMCs) by more than 500-fold using stimulation by an anti-CD3 monoclonal antibody with interleukin 15 (IL-15). These expanded and purified CD94-expressing cells attacked various malignant cell lines, including solid cancer cell lines, as well as the patients' leukemic cells but not autologous and allogeneic phytohemagglutinin (PHA) blasts in vitro. Also, these CD94-expressing cells prevented the growth of K562 leukemic cells and CW2 colon cancer cells in NOD/SCID mice in vivo. On the other hand, the CD94-expressing cells have low responsiveness to alloantigen in mixed lymphocyte culture (MLC) and have high transforming growth factor (TGF)-beta1- but low IL-2- producing capacity. Therefore, CD94-expressing cells with cytolytic activity against the recipient's leukemic and tumor cells without enhancement of alloresponse might be able to be expanded from donor G-PBMCs.
Volume 104(3)
Pages 768-74
Published 2004-8-1
DOI 10.1182/blood-2003-11-3870
PII S0006-4971(20)43605-5
PMID 15073036
MeSH Antigens, CD / blood Antigens, CD / genetics Antigens, CD / immunology* Base Sequence Cell Line, Tumor Cytotoxicity, Immunologic DNA Primers GPI-Linked Proteins Granulocyte Colony-Stimulating Factor / pharmacology Granulocyte-Macrophage Colony-Stimulating Factor / immunology* Hematopoietic Stem Cell Mobilization / methods Humans Interleukin-15 / immunology K562 Cells Lectins, C-Type / genetics Lectins, C-Type / immunology* Lipopolysaccharide Receptors / immunology Lymphocyte Activation Lymphocyte Culture Test, Mixed Membrane Proteins / immunology* NK Cell Lectin-Like Receptor Subfamily D Polymerase Chain Reaction Receptors, Immunologic / immunology* Recombinant Proteins Stem Cells / immunology* T-Lymphocytes / immunology*
IF 17.794
Resource
Human and Animal Cells K562(RCB0027) CW-2(RCB0778)