耐受原性疫苗可减少效应记忆 CD4 T 细胞，并诱导效应记忆 Treg 细胞，用于治疗 I 型糖尿病。

Tolerogenic vaccination reduced effector memory CD4 T cells and induced effector memory Treg cells for type I diabetes treatment.

机构信息

State Key Laboratory for Agro-Biotechnology, College of Biological Science, China Agricultural University, Beijing, China.

出版信息

PLoS One. 2013 Jul 19;8(7):e70056. doi: 10.1371/journal.pone.0070056. Print 2013.

BACKGROUND

Vaccination could induce immune tolerance and protected NOD mice from the development of type I diabetes (T1D). We previously demonstrated that insulin peptide (B9-23) combined with dexamethasone (DEX) stimulated the expansion of antigen specific regulatory T (Treg) cells which in turn effectively prevented T1D in NOD mice. Here, we aimed to investigate the therapeutic effect of tolerogenic vaccination for T1D treatment.

METHODOLOGY/PRINCIPAL FINDINGS: The diabetic NOD mice (Blood glucose level ≧250 mg/dl) were treated with B9-23 and DEX twice. The tolerance was restored by blocking maturation of dendritic cells (DCs) and inducing Treg cells in treated NOD mice. Remarkably, the reduction of autoreactive effector memory CD4 T (Tm) cells and the induction of functional effector memory Treg (mTreg) cells contributed to the improvement of T1D in treated NOD mice.

CONCLUSIONS/SIGNIFICANCE: Tolerogenic vaccination restored tolerance and ameliorated T1D by suppressing effector CD4 Tm cells and inducing effector mTreg cells. Our findings implicate the potential of tolerogenic vaccination for T1D treatment.

背景

疫苗接种可以诱导免疫耐受，并保护 NOD 小鼠免受 I 型糖尿病（T1D）的发展。我们之前的研究表明，胰岛素肽（B9-23）与地塞米松（DEX）联合刺激了抗原特异性调节性 T（Treg）细胞的扩增，进而有效地预防了 NOD 小鼠的 T1D。在这里，我们旨在研究免疫原性疫苗接种对 T1D 治疗的治疗效果。

方法/主要发现：患有糖尿病的 NOD 小鼠（血糖水平≧250mg/dl）接受 B9-23 和 DEX 两次治疗。在接受治疗的 NOD 小鼠中，通过阻断树突状细胞（DC）的成熟和诱导 Treg 细胞，恢复了耐受性。值得注意的是，自身反应性效应记忆 CD4 T（Tm）细胞的减少和功能性效应记忆 Treg（mTreg）细胞的诱导有助于改善治疗后的 NOD 小鼠的 T1D。

结论/意义：免疫原性疫苗接种通过抑制效应 CD4 Tm 细胞和诱导效应 mTreg 细胞来恢复耐受性并改善 T1D。我们的研究结果表明，免疫原性疫苗接种具有治疗 T1D 的潜力。