Iikuni Noriko, Lourenço Elaine V, Hahn Bevra H, La Cava Antonio
Division of Rheumatology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
J Immunol. 2009 Aug 1;183(3):1518-22. doi: 10.4049/jimmunol.0901163. Epub 2009 Jul 1.
In systemic lupus erythematosus (SLE), adaptive CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) suppress Th cells that help autoantibody (autoAb)-producing B cells. It is not known whether naturally occurring Tregs can directly suppress B cells in SLE without an intermediate suppression of Th cells. This aspect is important for its implications in the natural course of SLE, because most if not all of the clinical and pathologic effects in SLE are associated with a dysregulated production of autoAbs. In this study, we show that natural Tregs can inhibit B cell activity in vitro and in vivo in SLE through cell contact-mediated mechanisms that directly suppress autoAb-producing B cells, including those B cells that increase numerically during active disease. These results indicate that one way by which natural Tregs attempt to limit humoral autoimmunity in SLE is by directly targeting autoreactive B cells.
在系统性红斑狼疮(SLE)中,适应性CD4(+)CD25(+)Foxp3(+)调节性T细胞(Tregs)可抑制辅助产生自身抗体(autoAb)的B细胞的Th细胞。目前尚不清楚天然存在的Tregs在无Th细胞中间抑制作用的情况下能否直接抑制SLE中的B细胞。这一点对SLE的自然病程具有重要意义,因为SLE中大多数(如果不是全部)临床和病理效应都与自身抗体产生失调有关。在本研究中,我们发现天然Tregs可通过细胞接触介导的机制在体外和体内抑制SLE中的B细胞活性,该机制可直接抑制产生自身抗体的B细胞,包括在疾病活动期数量增加的那些B细胞。这些结果表明,天然Tregs试图限制SLE中体液自身免疫的一种方式是直接靶向自身反应性B细胞。