Recombinant TCR ligand reverses clinical signs and CNS damage of EAE induced by recombinant human MOG.
Recombinant TCR ligand reverses clinical signs and CNS damage of EAE induced by recombinant human MOG.
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DOI：
10.1007/s11481-009-9175-1
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发表时间：
2010-06
影响因子：
6.2
通讯作者：
Offner, Halina
中科院分区：
文献类型：
--
作者：
Sinha, Sushmita;Subramanian, Sandhya;Emerson-Webber, Ashley;Lindner, Maren;Burrows, Gregory G.;Grafe, Marjorie;Linington, Christopher;Vandenbark, Arthur A.;Bernard, Claude C. A.;Offner, Halina
越来越多的证据表明，除了T细胞依赖的效应机制外，自身抗体也参与了MS的发病，包括针对髓鞘少突胶质细胞糖蛋白(MOG)的脱髓鞘抗体。我们以前的研究已经证明，重组T细胞受体配体(RTL)对T细胞介导的实验性自身免疫性脑脊髓炎(EAE)具有非常有效的治疗作用。为了扩大多发性硬化症患者的RTL治疗范围，研究含有脱髓鞘抗体成分的RTL治疗EAE是很有意义的。因此，我们评价了T细胞特异性抗鼠(M)MOG-35-55多肽的RTL551对重组人(Rh)MOG诱导的C57BL/6小鼠EAE的治疗作用。我们报告，RTL551治疗可以逆转疾病进展，减少由重组人MOG引起的脱髓鞘和轴突损伤，而不抑制抗MOG抗体反应。这一结果表明，T细胞介导的炎症和相关的血脑屏障功能障碍是EAE发病的核心因素，这些关键因素的成功调控限制了脱髓鞘抗体的潜在损害。我们的研究结果支持使用RTL疗法治疗多发性硬化症患者，这些患者的疾病包括炎性T细胞以及具有额外抗体成分的患者。
Increasing evidence suggests that in addition to T cell dependent effector mechanisms, autoantibodies are also involved in the pathogenesis of MS, including demyelinating antibodies specific for myelin oligodendrocyte glycoprotein (MOG). Our previous studies have demonstrated that recombinant T cell receptor ligands (RTLs) are very effective for treating T cell mediated experimental autoimmune encephalomyelitis (EAE). In order to expand the scope of RTL therapy in MS patients, it was of interest to study RTL treatment of EAE involving a demyelinating antibody component. Therefore, we evaluated the therapeutic effects of RTL551, specific for T cells reactive to mouse (m)MOG-35-55 peptide, on EAE induced with recombinant human (rh)MOG in C57BL/6 mice. We report that RTL551 therapy can reverse disease progression and reduce demyelination and axonal damage induced by rhMOG without suppressing the anti-MOG antibody response. This result suggests that T cell mediated inflammation and associated blood-brain barrier dysfunction are the central contributors to EAE pathogenesis, and that successful regulation of these key players restricts potential damage by demyelinating antibodies. The results of our study lend support for the use of RTL therapy for treatment of MS subjects whose disease includes inflammatory T cells as well as those with an additional antibody component.
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影响因子：
5.3
作者：
Sinha, Sushmita;Subramanian, Sandhya;Offner, Halina
通讯作者：
Offner, Halina
影响因子：
4.4
作者：
Oliver, AR;Lyon, GM;Ruddle, NH
通讯作者：
Ruddle, NH
影响因子：
3.5
作者：
Chan, James;Ban, Ee Jun;Alderuccio, Frank
通讯作者：
Alderuccio, Frank
DOI：
10.1523/jneurosci.5812-08.2009
发表时间：
2009-03-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Sinha S;Subramanian S;Miller L;Proctor TM;Roberts C;Burrows GG;Vandenbark AA;Offner H
通讯作者：
Offner H
影响因子：
4.4
作者：
Burrows, GG;Chou, YK;Vandenbark, AA
通讯作者：
Vandenbark, AA