The Department of Microbiology and Immunology, East Carolina University, Greenville, NC, USA.
BMC Immunol. 2011 Dec 30;12:72. doi: 10.1186/1471-2172-12-72.
Vaccination strategies that elicit antigen-specific tolerance are needed as therapies for autoimmune disease. This study focused on whether cytokine-neuroantigen (NAg) fusion proteins could inhibit disease in chronic murine models of experimental autoimmune encephalomyelitis (EAE) and thus serve as potential therapeutic modalities for multiple sclerosis.
A fusion protein comprised of murine GM-CSF as the N-terminal domain and the encephalitogenic MOG35-55 peptide as the C-terminal domain was tested as a tolerogenic, therapeutic vaccine (TTV) in the C57BL/6 model of EAE. Administration of GMCSF-MOG before active induction of EAE, or alternatively, at the onset of EAE blocked the development and progression of EAE. Covalent linkage of the GM-CSF and MOG35-55 domains was required for tolerogenic activity. Likewise, a TTV comprised of GM-CSF and PLP139-151 was a tolerogen in the SJL model of EAE.
These data indicated that fusion proteins containing GM-CSF coupled to myelin auto-antigens elicit tolerance rather than immunity.
需要能够诱导抗原特异性耐受的疫苗接种策略作为自身免疫性疾病的治疗方法。本研究专注于细胞因子-神经抗原（NAg）融合蛋白是否可以抑制实验性自身免疫性脑脊髓炎（EAE）的慢性小鼠模型中的疾病，从而作为多发性硬化症的潜在治疗方式。
一种融合蛋白由鼠 GM-CSF 作为 N 端结构域和致脑炎 MOG35-55 肽作为 C 端结构域组成，作为治疗性疫苗（TTV）在 EAE 的 C57BL/6 模型中进行了测试。在主动诱导 EAE 之前或在 EAE 发作时给予 GMCSF-MOG 可阻止 EAE 的发生和进展。GM-CSF 和 MOG35-55 结构域的共价连接对于诱导耐受是必需的。同样，由 GM-CSF 和 PLP139-151 组成的 TTV 在 EAE 的 SJL 模型中也是一种耐受原。
这些数据表明，包含与髓鞘自身抗原偶联的 GM-CSF 的融合蛋白可诱导耐受而非免疫。
