Application of IgG-derived natural Treg epitopes (IgG Tregitopes) to antigen-specific tolerance induction in a murine model of type 1 diabetes.
Application of IgG-derived natural Treg epitopes (IgG Tregitopes) to antigen-specific tolerance induction in a murine model of type 1 diabetes.
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DOI：
10.1155/2013/621693
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发表时间：
2013
影响因子：
4.3
通讯作者：
De Groot AS
中科院分区：
文献类型：
--
作者：
Cousens LP;Su Y;McClaine E;Li X;Terry F;Smith R;Lee J;Martin W;Scott DW;De Groot AS
已报道IgG中的HLA II类限制性调节性T细胞（Treg）表位（也称为“Tregitopes”）通过刺激天然T细胞（nT细胞）的扩增来抑制对共同施用的抗原的免疫应答。在这里，我们评估他们对人体免疫反应的胰岛细胞抗原离体和1型糖尿病（T1 D）的小鼠模型在体内的调制的影响。Tregitopes和T1 D抗原的共同施用延迟了NOD小鼠中高血糖症的发展并降低了糖尿病的发病率。即使在发病后也可以观察到糖尿病的抑制。为了测量Tregitope治疗对T细胞反应的影响，我们评估了Tregitope治疗对DO 11.10小鼠的影响。用Tregitopes处理DO11.10小鼠后，观察到KJ 1 -26染色的OVA特异性CD 4 + T细胞中FoxP 3的上调，沿着抗OVA IG和T效应子应答的降低。在人T细胞的离体研究中，在Tregitope存在和不存在的情况下，外周血单核细胞（PBMC）对GAD 65表位的应答是可变的。Tregitope对GAD 65表位的离体免疫应答的抑制在使用来自新诊断的糖尿病受试者的PBMC的测定中似乎比其他更确定的糖尿病受试者更有效，并且证实了抑制程度与Tregitope的预测HLA限制的相关性。实施这些定义的调节性T细胞表位用于治疗T1 D和其他自身免疫性疾病可能导致疾病管理的范式转变。
HLA class II-restricted regulatory T cell (Treg) epitopes in IgG (also called “Tregitopes”) have been reported to suppress immune responses to coadministered antigens by stimulating the expansion of natural Tregs (nTregs). Here we evaluate their impact on human immune responses to islet cell antigens ex vivo and on the modulation of type 1 diabetes (T1D) in a murine model in vivo. Co-administration of Tregitopes and T1D antigens delayed development of hyperglycemia and reduced the incidence of diabetes in NOD mice. Suppression of diabetes could be observed even following onset of disease. To measure the impact of Tregitope treatment on T cell responses, we evaluated the effect of Tregitope treatment in DO11.10 mice. Upregulation of FoxP3 in KJ1-26-stained OVA-specific CD4+ T cells was observed following treatment of DO11.10 mice with Tregitopes, along with reductions in anti-OVA Ig and T effector responses. In ex vivo studies of human T cells, peripheral blood mononuclear cells' (PBMC) responses to GAD65 epitopes in the presence and absence of Tregitope were variable. Suppression of immune responses to GAD65 epitopes ex vivo by Tregitope appeared to be more effective in assays using PBMC from a newly diagnosed diabetic subject than for other more established diabetic subjects, and correlation of the degree of suppression with predicted HLA restriction of the Tregitopes was confirmed. Implementation of these defined regulatory T cell epitopes for therapy of T1D and other autoimmune diseases may lead to a paradigm shift in disease management.
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影响因子：
9.1
作者：
Maddur, Mohan S.;Othy, Shivashankar;Kaveri, Srini V.
通讯作者：
Kaveri, Srini V.
影响因子：
5.5
作者：
Gregory, Stephen H.;Mott, Stephanie;De Groot, Anne S.
通讯作者：
De Groot, Anne S.
影响因子：
13.6
作者：
Lopez, Marta;Clarkson, Michael R.;Najafian, Nader
通讯作者：
Najafian, Nader
影响因子：
4.8
作者：
Cousens, Leslie P.;Mingozzi, Federico;De Groot, Anne S.
通讯作者：
De Groot, Anne S.
影响因子：
1.5
作者：
DeGroot, AS;Jesdale, BM;Deocampo, G
通讯作者：
Deocampo, G