Division of Rheumatology at the David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Clin Immunol. 2012 Mar;142(3):291-5. doi: 10.1016/j.clim.2011.11.004. Epub 2011 Nov 15.
We have previously shown that immune tolerance induced by the anti-DNA Ig peptide pCons in (NZB×NZW)F(1) (NZB/W) lupus mice prolonged survival of treated animals and delayed the appearance of autoantibodies and glomerulonephritis. Part of the protection conferred by pCons could be ascribed to the induction of regulatory T cells (T(Reg)) that suppressed the production of anti-DNA antibodies in a p38 MAPK-dependent fashion. Here we show that another effect of pCons in the induction of immune tolerance in NZB/W lupus mice is the facilitation of effector T cell suppression by T(Reg). These new findings indicate that pCons exerts protective effects in NZB/W lupus mice by differentially modulating the activity of different T cell subsets, implying new considerations in the design of T(Reg)-based approaches to modulate T cell autoreactivity in SLE.
我们之前已经表明，抗 DNA Ig 肽 pCons 在（NZB×NZW）F1（NZB/W）狼疮小鼠中诱导的免疫耐受延长了治疗动物的存活时间，并延迟了自身抗体和肾小球肾炎的出现。pCons 赋予的部分保护作用可归因于诱导调节性 T 细胞（Treg），这些细胞以 p38 MAPK 依赖的方式抑制抗 DNA 抗体的产生。在这里，我们表明 pCons 在诱导 NZB/W 狼疮小鼠免疫耐受中的另一个作用是促进 Treg 对效应 T 细胞的抑制。这些新发现表明，pCons 通过差异调节不同 T 细胞亚群的活性在 NZB/W 狼疮小鼠中发挥保护作用，这意味着在设计基于 Treg 的方法来调节 SLE 中的 T 细胞自身反应时需要考虑新的因素。
