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The Journal of Immunology, 1998, 160: 1158-1165.
Copyright © 1998 by The American Association of Immunologists

The Ly-49 Family: Regulation of Cytotoxicity and Cytokine Production in Murine CD3+ Cells1

John R. Ortaldo2, Robin Winkler-Pickett, Anna T. Mason and Llewellyn H. Mason

Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702

The Ly-49 gene families are class I-recognizing receptors on murine NK cells. Most Ly-49 receptors inhibit NK cell lysis upon recognizing their target class I ligands. In this report we have examined the ability of Ly-49A and Ly-49G2 to regulate T cell functions on CD3+ cells, primarily the subset that also expresses NK-1.1 and/or DX5. The majority (>50%) of T cells that express Ly-49 molecules also coexpress NK-1.1 and/or DX5, although some NK-1.1- and/or DX5-/CD3+ cells express Ly-49 molecules. Lysis of target cells by IL-2-cultured T cells expressing Ly-49A and G2 was enhanced by Abs specific for Ly-49A and G2 as well as by Abs to class I (H-2Dd {alpha}1/{alpha}2). Murine T cells also were cultured in the presence of targets that express (H-2Dd) which is inhibiting for the Ly-49A and G2 receptors. These cells were examined for a coincident increase in cytokine production (IFN-{gamma}, TNF-{alpha}, and granulocyte-macrophage CSF). Abs to Ly-49A and G2 or their respective class I ligands blocked the negative signals mediated via the Ly-49 receptors and increased IFN-{gamma} and granulocyte-macrophage CSF production after interaction of these T cells with H-2Dd-expressing tumor targets. Furthermore, an EL-4 T cell line expressing both Ly-49A and G2, when treated with mAb YE148 and 4D11, demonstrated reduced cytokine production and calcium mobilization. These results demonstrate for the first time that Ly-49 class I binding receptors, previously thought to be restricted to mouse NK cells, can mediate important physiological functions of T cell subsets.




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