EFFECT OF ANTI-INTERFERON-GAMMA AND ANTI-INTERLEUKIN-2 MONOCLONAL-ANTIBODY TREATMENT ON THE DEVELOPMENT OF ACTIVELY AND PASSIVELY INDUCED EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN THE SJL/J MOUSE

EFFECT OF ANTI-INTERFERON-GAMMA AND ANTI-INTERLEUKIN-2 MONOCLONAL-ANTIBODY TREATMENT ON THE DEVELOPMENT OF ACTIVELY AND PASSIVELY INDUCED EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS IN THE SJL/J MOUSE
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DOI:
10.1016/0165-5728(92)90042-j
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发表时间:
1992-02-01
影响因子:
3.3
通讯作者:
STREJAN, GH
STREJAN, GH
中科院分区:
医学4区
文献类型:
--
作者:
DUONG, TT;STLOUIS, J;STREJAN, GH

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SJI。髓鞘碱性蛋白(MBP)完全弗氏佐剂(CFA)刺激小鼠仅发生发生率极低的轻度慢性复发实验性过敏性脑脊髓炎(EAE)。然而,用抗干扰素- γ (ifn - γ)单克隆抗体(mAb)治疗攻毒小鼠,在所有病例中确定了严重的疾病。同样,在被动EAE中,在转移时向体外mbp激活的细胞中添加抗ifn - γ会导致所有受体的疾病显著恶化。只有在主动攻击或被动转移时给予单抗才能观察到疾病增强作用,而在以后的时间则没有。抗白细胞介素-2 (IL-2)抗体在主动诱导中仅具有边际效应,但即使与增强疾病剂量的抗ifn - γ混合,也能显著减少被动EAE的表现。这些发现支持了IL-2是疾病诱导所必需的,而ifn - γ在EAE发展的早期起着疾病限制作用的观点。
SJI./J mice challenged with myelin basic protein (MBP) in complete Freund's adjuvant (CFA developed only mild chronic-relapsing experimental allergic encephalomyelitis (EAE) with very low incidence. However, treatment of challenged mice with anti-interferon-gamma (IFN-gamma) monoclonal antibody (mAb) determined severe disease in all cases. Similarly, in passive EAE, the addition of anti-IFN-gamma to the in vitro MBP-activated cells at the time of transfer led to significant disease exacerbation in all recipients. The disease enhancing effect was observed only when the mAb was given at the time of active challenge or of passive transfer, but not at later times. Anti-interleukin-2 (IL-2) antibody had only a marginal effect in the active induction, but drastically reduced the manifestations of passive EAE, even when mixed with a disease-enhancing dose of anti-IFN-gamma. These findings support the notion that IL-2 is required for disease induction whereas IFN-gamma plays a disease-limiting role early in the development of EAE.