脑脊髓炎
髓鞘碱性蛋白
细胞凋亡
髓鞘
肽
细胞生物学
实验性自身免疫性脑脊髓炎
免疫学
化学
生物
免疫系统
神经科学
多发性硬化
中枢神经系统
生物化学
作者
Bao‐Guo Xiao,Yu‐Min Huang,Lu Xu,Masahiko Ishikawa,Hans Link
标识
DOI:10.1016/s0165-5728(99)00041-7
摘要
Spontaneous remission of experimental allergic encephalomyelitis (EAE) is usually associated with prominent apoptosis. The mechanisms behind apoptosis are unknown. We examined the functions of dendritic cells (DC) from Lewis rats with EAE induced by immunization with myelin basic protein peptide 68–86 (). Recovery from EAE was associated with three major functional changes of freshly prepared DC: (1) elevated proliferation, (2) increased nitric oxide (NO) production, and (3) augmented IFN-γ secretion. In Freund's complete adjuvant (FCA)-immunized control rats, no increase of proliferation, NO production or IFN-γ secretion was observed on day 21 post-immunization (p.i.), i.e., recovery from EAE. In vitro effects of IFN-γ, TNF-α, TGF-β1, IL-4 and IL-10 on DC were examined. IFN-γ enhanced proliferation and NO production by DC, while TNF-α and IL-4 induced only slight DC proliferation. DC from recovering EAE rats (day 21 p.i.) suppressed -induced T cell proliferation compared to DC obtained at other time points in EAE and FCA-immunized rats. DC-derived NO induced apoptosis of CD4+ T cells, thereby inhibiting autoreactive T cell responses. Besides IFN-γ stimulation, NO production by DC was mainly induced in an antigen-dependent manner when DC were co-cultured with T cells. The results suggest that spontaneous recovery from EAE is associated with augmented DC functions. Overproduction of NO by DC results in apoptosis of autoreactive CD4+ T cells, thereby decreasing autoreactive T cell reactivities. The existence of such a NO negative feedback loop may contribute to remission of EAE.
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