Interleukin-15 stimulates macrophages to activate CD4+T cells: a role in the pathogenesis of rheumatoid arthritis?
| Autor: | René Rückert, Vadim Budagian, Silvia Bulfone-Paus, Claudia Metzler, Elena Csernok, Kathleen Marienfeld, Ralf Paus, Martin Ernst, Katja Brandt, Elena Bulanova |
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| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Genetically modified mouse Immunology Cell Cycle Proteins Mice Transgenic Biology Lymphocyte Activation Peripheral blood mononuclear cell Proinflammatory cytokine Arthritis Rheumatoid Pathogenesis Mice Phagocytosis Animals Humans Immunology and Allergy SOCS3 Cells Cultured Aged Cell Proliferation Interleukin-15 Antigen Presentation Messenger RNA Receptors Interleukin-15 Reverse Transcriptase Polymerase Chain Reaction Macrophages Histocompatibility Antigens Class II Cell Differentiation hemic and immune systems Original Articles Macrophage Activation Middle Aged Molecular biology Coculture Techniques In vitro Mice Inbred C57BL Interleukin 15 Female |
| Zdroj: | Immunology. 126:63-73 |
| ISSN: | 1365-2567 0019-2805 |
| DOI: | 10.1111/j.1365-2567.2008.02878.x |
| Popis: | Interleukin-15 (IL-15) is a proinflammatory cytokine that is overexpressed in rheumatoid arthritis (RA), a disease characterized by activation of monocytes/macrophages (MPhi), and by expansion of autoreactive CD4(+) T cells. We hypothesized that IL-15 plays a major role for this expansion of CD4(+) T cells and modulates the phenotype of monocytes/MPhi and their interaction with CD4(+) T cells. Here, we show that IL-15 enhances the proliferation of CD4(+) T cells from patients with RA in peripheral blood mononuclear cell cocultures. To further dissect the underlying mechanisms, we employed MPhi from IL-15(-/-) or IL-15 transgenic mice. These were induced to differentiate or were stimulated with IL-15. Here we show that addition of IL-15 during differentiation of MPhi (into 'IL-15MPhi') and overexpression of IL-15 by MPhi from IL-15(tg) mice leads to increased levels of major histocompatibility complex class II expression. This resulted in enhanced stimulation of antigen-specific CD4(+) T cells in vitro and was accompanied by reduced messenger RNA expression in MPhi for immunosuppressive SOCS3. The proliferation rates of IL-15MPhi and IL-15(tg)MPhi were high, which was reflected by increased p27(Kip1) and reduced p21(Waf1) levels. In view of high serum and synovial levels of IL-15 in patients with RA, our data suggest the possibility that this excess IL-15 in RA may stimulate monocytes/MPhi to activate the characteristic autoreactive CD4(+) T cells in RA. |
| Databáze: | OpenAIRE |
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