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| 論文調査委員 |
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| 学位授与大学 |
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Background Treatment with infliximab, a chimeric anti-tumor necrosis factor (TNF)-αantibody, is highly efficient in patients with inflammatory bowel disease (IBD). It neutralizessoluble TNF-α and indu...ces apoptosis of transmembrane TNF-α-positive macrophages and Tcells in the gut. Recently, T helper (Th) 17, as well as Th1, responses have been implicated inthe pathogenesis of IBD.Aims To clarify the effects of infliximab on Th1 and Th17 responses in vitro.Methods Naive CD4+ T cells isolated from peripheral blood of healthy volunteers werestimulated under Th1- or Th17-inducing conditions in the presence of 10 µg/ml of infliximabor control immunoglobulin G1 (IgG1). The concentrations of interferon (IFN)-γ, interleukin(IL)-17 and TNF-α in the culture supernatants were determined by enzyme-linkedimmunosorbent assays. Th1 and Th17 cells were immunostained with infliximab or controlIgG1 and transmembrane TNF-α-positive cells were analyzed by flow cytometry. Annexin Vstaining and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nickend labeling (TUNEL) assays were conducted to analyze the percentages of apoptotic cells.Results Both Th1 and Th17 cells expressed soluble and transmembrane TNF-α at comparablelevels. Although infliximab suppressed both IFN-γ secretion by Th1 cells and IL-17 secretionby Th17 cells, the level of suppression of IFN-γ production was more profound than that ofIL-17 production. Infliximab increased annexin V- and TUNEL-positive apoptotic cells under Th1-inducing conditions but not under Th17-inducing conditions. Conclusions Infliximab suppressed Th1 and Th17 differentiation in vitro, probably through different mechanisms. Th1 responses are more susceptible to infliximab-mediated immunosuppression than Th17 responses.続きを見る
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Mendeley出力
Th1 Responses Are More Susceptible