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Graft-Versus-Tumor Effects

Lack of IL-21 signal attenuates graft-versus-leukemia effect in the absence of CD8 T-cells

Bone Marrow Transplantation volume 46, pages 1557–1565 (2011)Cite this article

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Abstract

Previously, we have shown that IL-21R−/− splenocytes ameliorate GVHD as compared with wild-type splenocytes. Here, we investigated whether or not IL-21R−/− splenocytes diminish the graft-versus-leukemia (GVL) effect. Surprisingly, IL-21R−/− splenocytes efficiently eliminate leukemic cells as well as wild-type splenocytes, suggesting the retention of GVL effects in the absence of IL-21 signaling. To compare the GVL effect between IL-21R−/− and wild-type cells, we titrated the number of splenocytes required for the elimination of leukemic cells and found that the threshold of GVL effect was obtained between 5 × 105 and 5 × 106 with both types of splenocytes. Cotransplantation with CD8-depleted splenocytes but not with purified CD8 T-cells resulted in a significant reduction in anti-leukemic effect of IL-21R−/− cells compared with wild-type cells, suggesting that the lack of IL-21 signaling primarily impairs CD4 T-cell rather than CD8 T-cell function and the comparable GVL effect with IL-21R−/− bulk splenocytes results from cooperative compensation by CD8 T-cells.

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Acknowledgements

We thank Dr Tanabe (Institute of Medical Science, University of Tokyo, Tokyo) for donating the bcr-abl vector, Dr Kitamura (Institute of Medical Science, University of Tokyo, Tokyo) for donating PLAT-E, a packaging cell line and Drs Miyoshi (Tsukuba Institute, RIKEN, Tsukuba) and Okano (Keio University, Tokyo) for donating the luciferase-containing lentivirus vector. This work was supported in part by grants from the Ministry of Health, Labor and Welfare of Japan, by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by the Intramural Research Program of the National Heart, Lung and Blood Institute, National Institutes of Health (Bethesda, MD) and by a Young Investigator Award from Jichi Medical University, Tochigi, Japan.

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Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Jichi Medical University, Tochigi, Japan

    A Meguro, K Ozaki, K Hatanaka, I Oh, H Matsu, R Tatara, K Sato & K Ozawa

  2. Animal Research Center, Tokyo Medical University, Tokyo, Japan

    K Sudo

  3. Research Division of Cell and Molecular Medicine, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan

    T Ohmori & Y Sakata

  4. Frontier Research Initiative, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    S Nakae

  5. Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    W J Leonard

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Meguro, A., Ozaki, K., Hatanaka, K. et al. Lack of IL-21 signal attenuates graft-versus-leukemia effect in the absence of CD8 T-cells. Bone Marrow Transplant 46, 1557–1565 (2011). https://doi.org/10.1038/bmt.2010.342

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