A tumor-derived protein which provides T-cell costimulation through accessory cell activation
| Autor: | Randall Schreck, Terence Hui, Axel Ullrich, Laura K. Shawver, Mohammad Azam, T. J. Powell, Miloe McCall, Audie Rice, Harald App |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Interleukin 2
Cancer Research medicine.medical_treatment T-Lymphocytes Immunology Lipopolysaccharide Receptors Antigen-Presenting Cells Lymphocyte Activation Monocytes Cell Line Immune system medicine Concanavalin A Immunology and Allergy Cytotoxic T cell Humans Antigen-presenting cell Glycoproteins Pharmacology biology Interleukin-6 Monocyte Intercellular Adhesion Molecule-1 Recombinant Proteins Cell biology Culture Media Neoplasm Proteins Molecular Weight Nylons Cytokine medicine.anatomical_structure biology.protein Leukocytes Mononuclear Interleukin-2 Tumor necrosis factor alpha medicine.drug |
| Zdroj: | Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy. 17(4) |
| ISSN: | 1067-5582 |
| Popis: | A recently described tumor-derived glycoprotein, designated 90K, has been shown to have positive effects on the generation of cytotoxic effector cells (NK/LAK) from human PBMC. To determine the mechanism of these effects, we have examined the effects of 90K on cytokine production by human PBMC. A culture of normal PBMC with 90K alone did not result in IL-2 secretion; however, in coculture with suboptimal doses of ConA, 90K increased IL-2 secretion by PBMC. Coculture of PBMC with 90K and ConA also resulted in increased production of the cytokines IL-1, IL-6, GM-CSF, and TNF alpha. T cells depleted of accessory cells failed to respond to ConA alone, 90K alone, or the combination of ConA and 90K, suggesting that this protein does not have a direct effect on T cells. However, 90K alone was sufficient to induce cytokine production by unfractionated PBMC (IL-1, IL-6, GM-CSF, and TNF alpha) or by CD14-enriched PBMC (IL-1 and IL-6). In addition, expression of ICAM-1 was increased on a human monocytic cell line cultured with purified 90K in the absence of any other stimulus. This 90K-induced upregulation of ICAM-1 expression was accompanied by an increased accessory function of the monocytes, demonstrated by their ability to support ConA-induced activation of peripheral blood T cells. Based on the current data, we propose a model in which 90K activates accessory cells, resulting in the secretion of cytokines and the expression of adhesion molecules, which in turn act as costimulatory signals for T-cell activation. Activated T cells then produce cytokines such as IL-2, which lead to a more vigorous cell-mediated immune response to tumor cells and virus-infected cells. Thus, 90K shows promise as an immunotherapeutic reagent for diseases such as cancer and viral infection. |
| Databáze: | OpenAIRE |
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