Cytolytic activity and regulatory functions of inhibitory NK cell receptor-expressing T cells expanded from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells.
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.
Tanaka
Junji
J
Department of Hematology and Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Medicine, Sapporo Hokuyu Hospital, Sapporo, Japan. jutanaka@med.hokudai.ac.jp
Toubai
Tomomi
T
Tsutsumi
Yutaka
Y
Miura
Yoko
Y
Kato
Naoko
N
Umehara
Shintarou
S
Kahata
Kaoru
K
Mori
Akio
A
Toyoshima
Nobuyasu
N
Ota
Shuichi
S
Kobayashi
Takahiko
T
Kobayashi
Masanobu
M
Kasai
Masaharu
M
Asaka
Masahiro
M
Imamura
Masahiro
M
D015703:Antigens, CD / Q000097:blood / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D058851:GPI-Linked Proteins; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology; D020014:K562 Cells; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008565:Membrane Proteins / Q000276:immunology*; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000276:immunology*; D011994:Recombinant Proteins; D013234:Stem Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; C114505:CD160 protein, human; D017931:DNA Primers; D058851:GPI-Linked Proteins; D019409:Interleukin-15; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D008565:Membrane Proteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor