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Inhibition of Tumor Cell Proliferation by Natural Suppressor Cells Present in Murine Bone Marrow¹

Department of Pediatrics, All Children's Hospital, University of South Florida, St. Petersburg, Florida 33701 [K. S., E. E. S., R. A. G.]; First Department of Pathology, Kansai Medical University, Moriguchi, Osaka 570, Japan [K. S., M. I., H. O., R. Y., S. K., S. I.]; and Department of Zoology, Kyoto University, Kyoto 606, Japan [K. I.]

Natural suppressor (NS) cells, which are Thy-1^-, immunoglobulin^-, and nonadherent cells with relatively low density (1.063 to 1.075 g/ml), inhibit not only the proliferation of spleen cells which have been stimulated by allogeneic cells or mitogens but also the proliferation of tumor cell lines. Cell-to-cell contact is not necessary for NS cells to exert NS activity. Being radioresistant, DNA synthesis is not necessary for NS cells to suppress proliferation. However, protein synthesis is necessary, since puromycin blocks NS cell activity. In addition, NS cells were found to secrete a factor which inhibits DNA synthesis. Of the various cytokines tested, interleukin 3 and granulocyte-macrophage colony-stimulating factor enhance NS activity. These results suggest that NS cells play an important role in the suppression of not only immune responses but also tumor growth.

¹ This work was supported in part by American Cancer Society Institutional Grant 179-08; a grant from the Japanese Ministry of Health and Welfare; a grant from the Naito Foundation; a grant from the Mitsubishi Foundation; a grant-in-aid from the Mochida Memorial Foundation for Medical and Pharmaceutical Research; a grant from the Susuken Memorial Foundation; the Science Research Promotion Fund of the Japanese Private School Promotion Foundation (1987); Grant-in-Aid for Cancer Research 62015088 (1987); Grant-in-Aid for General Scientific Research 63480147 (1988) from the Japanese Ministry of Education, Science, and Culture; and Grants AG05628 and AI22360 from the NIH.

² To whom requests for reprints should be addressed.

Received 4/11/89. Revised 10/27/89.

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