Nasal administration of myelin basic protein prevents relapsing experimental autoimmune encephalomyelitis in DA rats by activating regulatory cells expressing IL-4 and TGF-beta mRNA

被引：51

作者：

Bai, XF ^{[1
]}

Shi, FD ^{[1
]}

Xiao, BG ^{[1
]}

Li, HL ^{[1
]}

vanderMeide, PH ^{[1
]}

Link, H ^{[1
]}

机构：

[1] BIOMED PRIMATE RES CTR,RIJSWIJK,NETHERLANDS

来源：

JOURNAL OF NEUROIMMUNOLOGY | 1997年 / 80卷 / 1-2期

关键词：

mucosal tolerance; experimental autoimmune encephalomyelitis; cytokine; IL-4; TGF-beta;

D O I：

10.1016/S0165-5728(97)00133-1

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

This study explores nasal administration of myelin basic protein (MBP) as a potential means of inducing tolerance to relapsing experimental autoimmune encephalomyelitis (PR-EAE), an experimental multiple sclerosis (MS) model that was induced in DA rats by immunization with rat spinal cord homogenate and incomplete Freund's adjuvant. DA rats received a total dosage of 0, 6, 60, 600 mu g/rat of bovine MBP on ten consecutive days prior to immunization. EAE with typical course was observed in control rats receiving only PBS nasally, and in rats receiving 6 mu g/rat of MBP. Rats receiving 60 mu g/rat of MBP developed acute EAE but no relapse during 60 days of observation post immunization (p.i.). Only one of eight rats receiving 600 mu g/rat of IL SBP developed slight, transient EAE. This protection was confirmed at the histology level and was associated with decreased levels of MBP-reactive IFN-gamma secreting Th1-like spleen cells on day 13 and 60 p.i. Rats receiving 60 and 600 mu g/rat of MBP showed decreased serum anti-MBP IgG2b antibody levels on day 60 p.i., and rats receiving 600 mu g/rat of MBP had marginally increased anti-MBP IgG1 antibody levels in serum compared to control EAE rats. Cytokine mRNA profiles in central nervous system (CNS) and spleen mononuclear cells were evaluated. Dose-dependent reduction of TNF-alpha mRNA expression were observed both in CNS and in splenocytes. Increased IL-4 and TGF-beta mRNA expression were observed in CNS of low (6 mu g/rat) and median (60 mu g/rat) dose of MBP tolerized rats and in splenotytes of rats tolerized with 600 mu g/rat of MBP. We conclude that nasal administration of MBP in DA rat prevents EAE induced by immunization with whole rat spinal cord homogenate that, besides MBP, contains multiple antigenic myelin proteins. A mechanism involving MBP-reactive regulatory cells expressing IL-4 and TGF beta mRNA acts as part in the induction of this tolerance. (C) 1997 Elsevier Science B.V.

引用

页码：65 / 75

页数：11

共 41 条

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