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 Blood, 15 December 2003, Vol. 102, No. 13, pp. 4456-4463.
Prepublished online as a Blood First Edition Paper on August 21, 2003; DOI 10.1182/blood-2003-07-2480.

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IMMUNOBIOLOGY

Two-signal requirement for activation and effector function of natural killer cell response to allogeneic tumor cells

Jian-Xin Gao, Xingluo Liu, Jing Wen, Michael A. Caligiuri, Iwona Stroynowski, Pan Zheng, and Yang Liu

From the Division of Cancer Immunology, Departments of Pathology and Medicine, The Ohio State University Comprehensive Cancer Center, Columbus; the Center for Immunology, Departments of Microbiology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas.

Optimal activation of T cells requires delivery of both antigenic and costimulatory signals. It is unclear, however, if the function of the natural killer (NK) cells is also modulated by these 2 signals. Here we report that efficient control of solid allogeneic tumors by NK cells depends on codelivery of both B7-1 and major histocompatibility complex (MHC) class I on the tumor cells. The codelivery is required for optimal expansion and effector function of NK cells in response to both melanoma and plasmocytoma that expressed allogeneic MHC class I. Our results demonstrate that the 2 signals required for T-cell function also can regulate NK immunity and reveal an important similarity between the innate NK response and the adaptive T-cell response. (Blood. 2003;102:4456-4463)


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