Transforming growth factor-β1 inhibits tumor necrosis factor-α/lymphotoxin production and adoptive transfer of disease by effector cells of autoimmune encephalomyelitis |
| |
Authors: | David B. Stevens Karen E. Gould Robert H. Swanborg |
| |
Abstract: | We previously reported that the CD4+ suppressor cells (Ts) that regulate recovery of Lewis rats from experimental autoimmune encephalomyelitis (EAE) produce transforming growth factor-β (TGF-β). We also reported that TGF-β downregulates interferon-γ (IFN-γ), but not interleukin-2 (IL-2) production, by the CD4+ effector T cells (Te) that mediate EAE. We now report that TGF-β also inhibits the production of tumor necrosis factor/lymphotoxin (TNF/LT) by EAE effector cells. When activated in vitro with myelin basic protein (MBP), Te produced TNF/LT, as measured using a WEHI 164 cytotoxicity assay. The specificity of cytokine action was demonstrated using neutralizing antibodies to TNF/LT. When added to the Te + MBP cultures, TGF-β inhibited TNF/LT production in a dose-dependent fashion. Moreover, neutralizing anti-TGF-β antibodies augmented TNF/LT production in the Te + MBP cultures. We also confirm that TGF-β inhibits adoptive transfer of EAE. In contrast, murine IL-10 only partially inhibited TNF/LT and IFN-γ production by Te. We conclude that TGF-β production by Ts plays a major role in recovery from EAE in the Lewis rat by inhibiting TNF/LT and IFN-γ production by the effector cells that mediate EAE. |
| |
Keywords: | Transforming growth factor-β Lymphotoxin Tumor necrosis factor Myelin basic protein MTT (( ((3-(4,5)-dimethylthiazol-2-yl)-2,5,-diphenyl-tetrazolium bromide) |
本文献已被 ScienceDirect 等数据库收录! |
|