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CD94 Defines Phenotypically and Functionally Distinct Mouse NK Cell Subsets¹

Jianhua Yu,^2* Min Wei,^* Hsiaoyin Mao,^* Jianying Zhang, Tiffany Hughes,^* Takeki Mitsui,^* Il-kyoo Park,^* Christine Hwang,^* Shujun Liu,^* Guido Marcucci,^* Rossana Trotta,^* Don M. Benson, Jr.,^* and Michael A. Caligiuri^2*

^*Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210; Division of Hematology/Oncology, Department of Internal Medicine, The Ohio State Universit0y, Columbus, OH 43210; Center for Biostatistics, The Ohio State University, Columbus, OH 43210; and The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute, Columbus, OH 43210

Understanding of heterogeneous NK subsets is important for the study of NK cell biology and development, and for the application of NK cell-based therapies in the treatment of disease. Here we demonstrate that the surface expression of CD94 can distinctively divide mouse NK cells into two approximately even CD94^low and CD94^high subsets in all tested organs and tissues. The CD94^high NK subset has significantly greater capacity to proliferate, produce IFN-, and lyse target cells than does the CD94^low subset. The CD94^high subset has exclusive expression of NKG2A/C/E, higher expression of CD117 and CD69, and lower expression of Ly49D (activating) and Ly49G2 (inhibitory). In vivo, purified mouse CD94^low NK cells become CD94^high NK cells, but not vice versa. Collectively, our data suggest that CD94 is an Ag that can be used to identify functionally distinct NK cell subsets in mice and could also be relevant to late-stage mouse NK cell development.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Cancer Institute Grants CA95426 and CA68458 (to M.A.C).

² Address correspondence and reprint requests to Dr. Michael A. Caligiuri or Dr. Jianhua Yu, Ohio State University, 300 West 10th Avenue, Suite 521C, Columbus, OH 43210. E-mail address: michael.caligiuri{at}osumc.edu or jianhua.yu{at}osumc.edu

³ Abbreviations used in this paper: WT, wild type; mIL-12, murine IL-12.

⁴ The online version of this article contains supplemental material.