The Ly-49 Family - Regulation of Cytotoxicity and Cytokine Production in Murine Cd3(+) Cells

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 ne 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 bg 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-2D(d) alpha 1/alpha 2). Murine T cells also were cultured in the presence of targets that express (H-2D(d)) which is inhibiting for the Ly-49A and GZ 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-2D(d)-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. [References: 30]

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