Tolerance induction in EAE by epicutaneous immunization

通过表皮免疫诱导 EAE 耐受

基本信息

批准号：
7117348
负责人：
Margaret S. Bynoe
金额：
$ 10.8万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-01 至 2007-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The human disease multiple sclerosis (MS) is an inflammatory and demyelinating neurological disease that is mediated by T helper-1 (Th1) cells. Experimental allergic encephalomyelitis (EAE) is the most well-established animal model for the study of MS. EAE can be actively induced in certain inbred mouse strains following immunization with myelin protein autoantigens such as myelin basic protein (MBP), proteolipid protein (PLP) or myelin oligodendrocyte protein (MOG) in adjuvant. Recently, we found that when we immunize transgenic mice carrying a MBP specific T cell receptor via the epicutaneous (skin) route with MBP peptides in a patch prior to immunizing them with the same peptide to induce disease, such mice were protected from EAE. This protection was antigen-specific, antigen dose-dependent and was mediated by CD4 T cells that transferred protection to naive recipients. In addition, epicutaneous immunization with myelin-derived self-peptides protected normal mice from developing EAE in an antigen-specific and antigen dose-dependent manner including in a relapsing-remitting model of the disease. However, when these same mice are epicutaneously immunized with their cognate peptide in adjuvant, disease was accelerated. This proposal describes three specific aims that will attempt to elucidate the mechanism(s) by which the epicutaneous administration of self-peptide induces dominant tolerance in mice. Some aims focus on determining the role of skin dendritic cells in the induction of tolerance in both the transgenic and non-transgenic mouse models. Proposed studies will also investigate the mechanism(s) by which tolerance is induced and operates in normal mice. In normal mice, we will explore whether Th2 cytokines are involved in mediating protection from disease: specifically in the (SJLxPL/J)F 1 mouse model. Finally, we will carry out experiments to test whether epicutaneous immunization with autoantigenic peptides is capable of ameliorating EAE.

描述（由申请人提供）：人类疾病多发性硬化症 (MS) 是一种由 T 辅助细胞 (Th1) 介导的炎症性脱髓鞘神经疾病。实验性过敏性脑脊髓炎 (EAE) 是研究 MS 的最完善的动物模型。在用髓磷脂蛋白自身抗原（例如髓磷脂碱性蛋白（MBP）、蛋白脂质蛋白（PLP）或髓磷脂少突胶质细胞蛋白（MOG））进行佐剂免疫后，某些近交系小鼠品系可以主动诱导EAE。最近，我们发现，当我们通过表皮（皮肤）途径用贴片中的 MBP 肽对携带 MBP 特异性 T 细胞受体的转基因小鼠进行免疫，然后用相同的肽对它们进行免疫以诱导疾病时，这些小鼠可以免受 EAE 的侵害。这种保护是抗原特异性的、抗原剂量依赖性的，并且由 CD4 T 细胞介导，将保护转移给初始接受者。此外，使用髓鞘源性自肽进行表皮免疫可以以抗原特异性和抗原剂量依赖性方式保护正常小鼠免于发生EAE，包括在该疾病的复发缓解模型中。然而，当这些相同的小鼠用佐剂中的同源肽进行表皮免疫时，疾病加速。该提案描述了三个具体目标，试图阐明经皮施用自肽诱导小鼠显性耐受的机制。一些目标集中于确定皮肤树突状细胞在转基因和非转基因小鼠模型中诱导耐受性中的作用。拟议的研究还将调查正常小鼠中诱导和发挥耐受性的机制。在正常小鼠中，我们将探讨 Th2 细胞因子是否参与介导疾病保护：特别是在 (SJLxPL/J)F 1 小鼠模型中。最后，我们将进行实验来测试自身抗原肽的表皮免疫是否能够改善 EAE。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Control of experimental autoimmune encephalomyelitis by CD4+ suppressor T cells: peripheral versus in situ immunoregulation.

CD4 抑制 T 细胞控制实验性自身免疫性脑脊髓炎：外周免疫调节与原位免疫调节。

DOI：
发表时间：
2007-11
期刊：
影响因子：
3.3
作者：
Bynoe, Margaret S;Bonorino, Paula;Viret, Christophe
通讯作者：
Viret, Christophe

Neuropilin-1 attenuates autoreactivity in experimental autoimmune encephalomyelitis.

Neuropilin-1 减弱实验性自身免疫性脑脊髓炎的自身反应性。

DOI：
发表时间：
2011-02-01
期刊：
影响因子：
11.1
作者：
Solomon, Benjamin D;Mueller, Cynthia;Chae, Wook;Alabanza, Leah M;Bynoe, Margaret S
通讯作者：
Bynoe, Margaret S

Adenosine receptor signaling: a key to opening the blood-brain door.

腺苷受体信号传导：打开血脑之门的钥匙。

DOI：
发表时间：
2015-09-02
期刊：
影响因子：
0
作者：
Bynoe, Margaret S;Viret, Christophe;Yan, Angela;Kim, Do
通讯作者：
Kim, Do

A tale of two STAT6 knock out mice in the induction of experimental autoimmune encephalomyelitis.

两只 STAT6 敲除小鼠诱导实验性自身免疫性脑脊髓炎的故事。

DOI：
发表时间：
2009-01-03
期刊：
影响因子：
3.3
作者：
Wang, Yongmei;Evans, J T;Rodriguez, Frederick;Fields, Patrick;Mueller, Cynthia;Chitnis, Tanuja;Khoury, Samia J;Bynoe, Margaret S
通讯作者：
Bynoe, Margaret S

Foxp3+CD4+ T cell-mediated immunosuppression involves extracellular nucleotide catabolism.

Foxp3 CD4 T 细胞介导的免疫抑制涉及细胞外核苷酸分解代谢。