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Interleukin‐15 stimulates macrophages to activate CD4 + T cells: a role in the pathogenesis of rheumatoid arthritis?
Author(s) -
Rückert René,
Brandt Katja,
Ernst Martin,
Marienfeld Kathleen,
Csernok Elena,
Metzler Claudia,
Budagian Vadim,
Bulanova Elena,
Paus Ralf,
BulfonePaus Silvia
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.02878.x
Subject(s) - proinflammatory cytokine , immunology , biology , cytokine , t cell , interleukin 21 , major histocompatibility complex , arthritis , microbiology and biotechnology , inflammation , antigen , immune system
Summary Interleukin‐15 (IL‐15) is a proinflammatory cytokine that is overexpressed in rheumatoid arthritis (RA), a disease characterized by activation of monocytes/macrophages (MΦ), 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/MΦ 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 MΦ 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 MΦ (into ‘IL‐15MΦ’) and overexpression of IL‐15 by MΦ 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 MΦ for immunosuppressive SOCS3. The proliferation rates of IL‐15MΦ and IL‐15 tg MΦ 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/MΦ to activate the characteristic autoreactive CD4 + T cells in RA.