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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
1/
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-
, TNF-
, 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-
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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