THE LY-49 FAMILY - REGULATION OF CYTOTOXICITY AND CYTOKINE PRODUCTIONIN 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 th eir target class I ligands, In this report ne have examined the abilit y 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 majori ty (>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 expre ss Ly-49 molecules, Lysis of target cells bg IL-2-cultured T cells exp ressing Ly-49A and G2 was enhanced by Abs specific for Ly-49A and G2 a s 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)) w hich is inhibiting for the Ly-49A and GZ receptors, These cells were e xamined for a coincident increase in cytokine production (IFN-gamma, T NF-alpha, and granulocyte-macrophage CSF). Abs to Ly-49A and G2 or the ir respective class I ligands blocked the negative signals mediated vi a the Ly-49 receptors and increased IFN-gamma and granulocyte-macropha ge CSF production after interaction of these T cells with H-2D(d)-expr essing tumor targets, Furthermore, an EL-4 T cell line expressing both Ly-49A and G2, when treated with mAb YE148 and 4D11, demonstrated red uced cytokine production and calcium mobilization, These results demon strate for the first time that Ly-49 class I binding receptors, previo usly thought to be restricted to mouse NK cells, can mediate important physiological functions of T cell subsets.