T-cell cytotoxicity of human Schwann cells: TNFalpha promotes fasL-mediated apoptosis and IFN gamma perforin-mediated lysis
| Autor: | Paola Valdo, E. Nardelli, Bruno Bonetti, Silvia Marconi, Giovanni Ossi, Barbara Masotto, Luca De Toni, Nicolo' Rizzuto, Giuseppe Moretto |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Pore Forming Cytotoxic Proteins
Fas Ligand Protein immune privilege medicine.medical_treatment Blotting Western chemical and pharmacologic phenomena Biology Fas ligand Cellular and Molecular Neuroscience Interferon-gamma Jurkat Cells Immune system Interferon peripheral nervous system apoptosis Schwann cells T-lymphocytes medicine In Situ Nick-End Labeling Cytotoxic T cell Humans Interferon gamma Lymphocytes fas Receptor Cells Cultured Membrane Glycoproteins Perforin Tumor Necrosis Factor-alpha Neuroma Acoustic Flow Cytometry Immunohistochemistry Cytokine Neurology Polyradiculoneuropathy Chronic Inflammatory Demyelinating Immunology Cancer research biology.protein Tumor necrosis factor alpha medicine.drug T-Lymphocytes Cytotoxic |
| Popis: | The ability of resident cells to induce apoptosis of invading immune cells is a major regulatory factor operating in immune-privileged tissues, including the nervous system. We investigated the cellular and molecular factors participating in modulation of immune response in peripheral nerves, focusing on two cytotoxic pathways: fas ligand (fasL) and perforin. fasL and perforin expression was found by immunochemistry on Schwann cells (Sc) in nerve biopsies from patients with chronic inflammatory demyelinating polyneuritis and on human Sc cultures. Treatment of Sc with tumor necrosis factor (TNF) alpha and interferon (IFN) gamma upregulated the expression of both molecules. In a coculture model, Sc exposed to TNFalpha or IFN gamma were able to induce both apoptotic and lytic injury of T-lymphocytes. Inactivation of fasL with the neutralizing antibody NOK-2 abolished T-cell apoptosis induced by Sc treated with TNFalpha, but not by Sc treated with IFN gamma. Conversely, T-cell lysis was significantly decreased when IFN gamma-activated Sc were treated with concanamycin A, which inhibited perforin release. At variance with T-lymphocytes, B-cells were less sensitive to cytokine-treated Sc toxicity. Thus, Sc exposed to inflammatory cytokines have the capacity of inducing selective damage of T-lymphocytes and have the potential of regulating the immune response in the peripheral nervous system. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|