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Blood, 1 August 2004, Vol. 104, No. 3, pp. 768-774.
Prepublished online as a Blood First Edition Paper on April 8, 2004; DOI 10.1182/blood-2003-11-3870.
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Submitted November 13, 2003
Accepted March 26, 2004
Cytolytic activity and regulatory functions of inhibitory NK cell receptor-expressing T cells expanded from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells
Junji Tanaka*, Tomomi Toubai, Yutaka Tsutsumi, Yoko Miura, Naoko Kato, Shintarou Umehara, Kaoru Kahata, Akio Mori, Nobuyasu Toyoshima, Shuichi Ota, Takahiko Kobayashi, Masanobu Kobayashi, Masaharu Kasai, Masahiro Asaka, and Masahiro Imamura
Hematology and Oncology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Third Department of Internal Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Cancer Pathobiology, Institute for Genetic Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan
Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan
* Corresponding author; email: jutanaka{at}med.hokudai.ac.jp.
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 G-CSF-mobilized peripheral blood mononuclear cells (G-PBMCs) by more than 500 fold using stimulation by an anti-CD3 monoclonal antibody with 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 PHA blasts in vitro. Also, these CD94-expressing cells prevented the growth of K562 leukemic cells and also CW2 colon cancer cells in NOD/SCID mice in vivo. On the other hand, the CD94-expressing cells have low responsiveness to alloantigen in MLC and also have high TGF- 1- 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.
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