The Ly-49 family: regulation of cytotoxicity and cytokine production in murine CD3+ cells.

Abstract

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.

• Authors: J R Ortaldo, R Winkler-Pickett, A T Mason, L H Mason
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 160 Issue 3 Pg. 1158-65 (Feb 01 1998) ISSN: 0022-1767 [Print] United States
• PMID: 9570529 (Publication Type: Journal Article)

Chemical References

• Antigens
• Antigens, Ly
• Antigens, Surface
• CD3 Complex
• Carrier Proteins
• Cytokines
• Klrb1c protein, mouse
• Lectins, C-Type
• Membrane Glycoproteins
• Membrane Proteins
• NK Cell Lectin-Like Receptor Subfamily B
• Proteins
• Receptors, Immunologic
• Receptors, NK Cell Lectin-Like

Topics

• Animals
• Antigens (biosynthesis)
• Antigens, Ly
• Antigens, Surface (immunology, metabolism, physiology)
• CD3 Complex (biosynthesis)
• Carrier Proteins (biosynthesis)
• Cytokines (biosynthesis)
• Cytotoxicity, Immunologic
• Killer Cells, Natural (metabolism)
• Lectins, C-Type
• Liver (immunology, metabolism)
• Membrane Glycoproteins (biosynthesis, metabolism, physiology)
• Membrane Proteins (biosynthesis)
• Mice
• Mice, Inbred C57BL
• NK Cell Lectin-Like Receptor Subfamily B
• Protein Biosynthesis
• Proteins
• Receptors, Immunologic (biosynthesis, physiology)
• Receptors, NK Cell Lectin-Like
• Spleen (immunology, metabolism)
• T-Lymphocyte Subsets (immunology, metabolism)