ICAM-1 and LFA-3 enhance the ability of anti-CD3 mAb to stimulate interferon gamma production in interleukin-2-activated T cells.

Abstract

Interleukin-2 (IL-2)-activated killer cells, also referred to as lymphokine-activated killer (LAK) cells, are stimulated by tumor cells to express cytotoxic activity and to also secrete cytokines such as interferon gamma (IFN gamma) and tumor necrosis factor alpha (TNF alpha). We previously reported that secretion of cytokines by IL-2-activated T cells (LAK-T cells) is dependent on the initial cross-linking of the T cell receptor (TCR)-CD3-molecular complex, but the cross-linking of accessory molecules, such as LFA-1, CD2, CD44 and CD45, on LAK-T cells can enhance this cytokine production. We have developed an approach involving interspecific gene transfer to define further the contributions of LFA-1 and CD2 to the activation of LAK-T cells. The genes for huICAM-1 (a ligand for LFA-1) and huLFA-3 (a ligand for CD2) were transfected singly and in combination into a null mouse melanoma background, and clonal populations of cells that stably express ICAM-1 and/or LFA-3 were derived. Expression of the introduced ICAM-1 and/or LFA-3 by transfected cells enhanced their ability to bind LAK-T cells; the LFA-1/ICAM-1-mediated binding was not further enhanced by activation with phorbol 12-myristate 13-acetate. ICAM-1- and/or LFA-3-transfected cells, in the presence of immobilized anti-CD3, exhibited a greater ability to stimulate IFN gamma secretion by LAK-T cells compared to the untransfected parental lines. This experimental system, which allows ICAM-1/LFA-1 and CD2/LFA-3 interactions to occur on the LAK-T cell at a site distal from the anti-CD3 signal, extends our understanding of LAK-T cell activation by establishing that both LFA-1/ICAM-1 and CD2/LFA-3 can mediate co-stimulation via adhesion and signaling events.

• Authors: A S Chong, X L Jiang, P Scuderi, M Lamas, L H Graf Jr
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 39 Issue 2 Pg. 127-34 (Aug 1994) ISSN: 0340-7004 [Print] Germany
• PMID: 7519126 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antigens, CD
• Antigens, Differentiation, T-Lymphocyte
• CD2 Antigens
• CD3 Complex
• CD58 Antigens
• Cell Adhesion Molecules
• Interleukin-2
• Membrane Glycoproteins
• Receptors, Immunologic
• Intercellular Adhesion Molecule-1
• Interferon-gamma

Topics

• Antibodies, Monoclonal (pharmacology)
• Antigens, CD (genetics, physiology)
• Antigens, Differentiation, T-Lymphocyte (genetics, physiology)
• CD2 Antigens
• CD3 Complex (immunology)
• CD58 Antigens
• Cell Adhesion (physiology)
• Cell Adhesion Molecules (genetics, physiology)
• Humans
• Intercellular Adhesion Molecule-1
• Interferon-gamma (biosynthesis)
• Interleukin-2 (pharmacology)
• Killer Cells, Lymphokine-Activated (cytology, drug effects, metabolism)
• Lymphocyte Activation (drug effects)
• Membrane Glycoproteins (genetics, physiology)
• Phenotype
• Receptors, Immunologic (genetics, physiology)
• Stimulation, Chemical
• T-Lymphocytes (cytology, drug effects, metabolism)
• Transfection