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 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 alpha1/alpha2). 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.
Ortaldo
J R
JR
Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702, USA.
Winkler-Pickett
R
R
Mason
A T
AT
Mason
L H
LH
D000818:Animals; D000941:Antigens / Q000096:biosynthesis; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D017252:CD3 Complex / Q000096:biosynthesis*; D002352:Carrier Proteins / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D007694:Killer Cells, Natural / Q000378:metabolism; D037181:Lectins, C-Type; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D014176:Protein Biosynthesis; D011506:Proteins; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology; D055630:Receptors, NK Cell Lectin-Like; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D017252:CD3 Complex; D002352:Carrier Proteins; D016207:Cytokines; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like