Karpus W J, Kennedy K J, Smith W S, Miller S D
Department of Microbiology and Immunology, Northwestern University Medical School, Chicago, IL 60611, USA.
J Neurosci Res. 1996 Aug 15;45(4):410-23. doi: 10.1002/(SICI)1097-4547(19960815)45:4<410::AID-JNR10>3.0.CO;2-4.
Peripheral antigen-specific tolerance can be induced by feeding protein antigens. The mechanism has been described as either clonal anergy/deletion or induction of antigen-specific regulatory cells that produce transforming growth factor-beta (TGF-beta). These two mechanisms have been linked to the magnitude and frequency of the dose of antigen fed; a single high dose induces anergy/deletion, whereas multiple low doses of antigen induce TGF-beta-secreting regulatory cells. In the present study, we investigated the mechanisms of feeding soluble peptides of proteolipid protein (PLP) for prevention of experimental autoimmune encephalomyelitis (EAE) induced by either intact PLP or the immunodominant PLP139-151 peptide. Feeding PLP139-151 prevented acute and relapsing EAE induced by either PLP139-151 or intact PLP. PLP139-151 feeding induced anergy in the T helper 1 (Th1) population as measured by an inhibition of both proliferation and interferon-gamma (IFN-gamma) production. Interleukin-4 (IL-4) production was increased, but increased TGF-beta production was not observed. Importantly, PLP139-151 feeding induced anergy in peripheral and central nervous system (CNS)-in-filtrating T cells. Feeding of the subdominant PLP epitope (PLP178-191) failed to inhibit EAE induced by PLP139-151; therefore, oral tolerance was not due to induction of bystander suppression. These results demonstrate that both acute and relapsing paralysis in EAE can be prevented by feeding the immunodominant peptide of PLP.
通过喂食蛋白质抗原来诱导外周抗原特异性耐受。其机制被描述为克隆无能/缺失或诱导产生转化生长因子-β（TGF-β）的抗原特异性调节细胞。这两种机制与喂食抗原剂量的大小和频率有关；单次高剂量诱导无能/缺失，而多次低剂量抗原诱导分泌TGF-β的调节细胞。在本研究中，我们研究了喂食蛋白脂蛋白（PLP）的可溶性肽预防由完整PLP或免疫显性PLP139 - 151肽诱导的实验性自身免疫性脑脊髓炎（EAE）的机制。喂食PLP139 - 151可预防由PLP139 - 151或完整PLP诱导的急性和复发性EAE。通过抑制增殖和干扰素-γ（IFN-γ）产生来测量，喂食PLP139 - 151可诱导辅助性T细胞1（Th1）群体出现无能。白细胞介素-4（IL-4）产生增加，但未观察到TGF-β产生增加。重要的是，喂食PLP139 - 151可诱导外周和中枢神经系统（CNS）浸润性T细胞出现无能。喂食亚显性PLP表位（PLP178 - 191）未能抑制由PLP139 - 151诱导的EAE；因此，口服耐受不是由于旁观者抑制的诱导。这些结果表明，通过喂食PLP的免疫显性肽可预防EAE中的急性和复发性麻痹。
