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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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IMMUNOBIOLOGY

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

From the Department of Hematology and Oncology, Third Department of Internal Medicine, Cancer Pathobiology, Institute for Genetic Medicine, Hokkaido University Graduate School of Medicine, Sapporo Hokuyu Hospital, Sapporo, Japan.

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 colonystimulating 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)–{beta}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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