Anti-Tumor Necrosis Factor-alpha Antibodies Induce Regulatory Macrophages in an Fc Region-Dependent Manner
| Autor: | Manon E. Wildenberg, Daniel W. Hommes, Anne Christine W. Vos, Auke P. Verhaar, Marjolijn Duijvestein, Gijs R. van den Brink |
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| Přispěvatelé: | AII - Amsterdam institute for Infection and Immunity, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Gastroenterology and Hepatology |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
T-Lymphocytes
Anti-Inflammatory Agents Apoptosis Receptors Cell Surface Receptors Fc Biology Antibodies Monoclonal Humanized Lymphocyte Activation Certolizumab Receptors Tumor Necrosis Factor Regulatory macrophages Etanercept Polyethylene Glycols Immunoglobulin Fab Fragments Crohn Disease Humans Macrophage Lectins C-Type Antigen-presenting cell Cells Cultured Cell Proliferation Hepatology Caspase 3 Tumor Necrosis Factor-alpha Macrophages Adalimumab Gastroenterology Antibodies Monoclonal Dendritic cell Fragment crystallizable region Infliximab Immunoglobulin Fc Fragments Mannose-Binding Lectins Immunoglobulin G Immunology Certolizumab Pegol Leukocytes Mononuclear Cancer research Cytokines Cytokine secretion Tumor necrosis factor alpha Immunosuppressive Agents Mannose Receptor Type 2 Macrophage Inflammatory Response IBD Autoimmunity inflammatory-bowel-disease placebo-controlled trial active crohns-disease monoclonal-antibody double-blind tnf-alpha t-lymphocytes accent-i infliximab polymorphism |
| Zdroj: | Gastroenterology, 140(1), 221 Gastroenterology, 140(1), 221-230. W.B. Saunders Ltd |
| ISSN: | 0016-5085 |
| Popis: | BACKGROUND & AIMS: Anti-tumor necrosis factor (TNF)alpha antibodies are effective in treating patients with Crohn's disease whereas soluble TNF alpha receptors have not shown clinical efficacy; the mechanism that underlies these different effects is not clear. We examined the immunosuppressive effects of different anti-TNF alpha reagents on activated T cells. METHODS: We studied the effects of anti-TNF alpha antibodies infliximab and adalimumab, the soluble TNF alpha receptor etanercept, the pegylated F(ab') fragment certolizumab, and certolizumab-immunoglobulin (Ig)G on primary activated T cells. T cells were grown in isolation or in a mixed lymphocyte reaction (MLR). Proliferation was measured by H-3 thymidine incorporation and apoptosis was examined using Annexin V labeling and a colorimetric assay for activated caspase-3. Macrophage phenotypes were assayed by flow cytometry and cytokine secretion. RESULTS: Infliximab and adalimumab reduced T-cell proliferation in an MLR whereas etanercept and certolizumab did not; this effect was lost after Fc receptors were blocked. The infliximab F(ab') 2 fragment did not inhibit proliferation whereas certolizumab-IgG did inhibit proliferation. In the MLR, the antibodies against TNF induced formation of a new population of macrophages in an Fc region-dependent manner; these macrophages had an immunosuppressive phenotype because they inhibit proliferation of activated T cells, produce anti-inflammatory cytokines, and express the regulatory macrophage marker CD206. CONCLUSIONS: Regulatory macrophages have immunosuppressive properties and an important role in wound healing. Antibodies against TNF induce regulatory macrophages in an Fc region-dependent manner. These functions of anti-TNFs might contribute to the resolution of inflammation. |
| Databáze: | OpenAIRE |
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