Sthoeger Z M, Dayan M, Tcherniack A, Green L, Toledo S, Segal R, Elkayam O, Mozes E
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Clin Exp Immunol. 2003 Feb;131(2):385-92. doi: 10.1046/j.1365-2249.2003.02058.x.
Two peptides, based on the sequences of the complementarity-determining regions (CDR) 1 and 3 of a pathogenic murine monoclonal anti-DNA autoatibody that bears the 16/6 idiotype (Id), were shown to either prevent or treat an already established systemic lupus erythematosus (SLE) in two murine models of lupus. Two additional peptides based on the human monoclonal anti-DNA, 16/6 Id were synthesized. This study was undertaken in order to investigate the ability of the CDR-based peptides to immunomodulate SLE-associated responses of peripheral blood lymphocytes (PBL) of SLE patients. PBL of 24 of the 62 SLE patients tested proliferated in vitro following stimulation with the human 16/6 Id. Peptides based on the CDRs of both the human and murine anti-DNA autoantibodies inhibited efficiently and specifically the 16/6 Id-induced proliferation and IL-2 production. The latter inhibitions correlated with an up-regulated production (by 2.5-3.5-fold) of the immunosuppressive cytokine, TGF-beta. Overall, the results of our study demonstrate that the CDR-based peptides are capable of down-regulating in vitro autoreactive T cell responses of PBL of SLE patients. Thus, these peptides are potential candidates for a novel specific treatment of SLE patients.
基于一种携带16/6独特型（Id）的致病性小鼠单克隆抗DNA自身抗体互补决定区（CDR）1和3序列的两种肽，在两种狼疮小鼠模型中显示出可预防或治疗已确立的系统性红斑狼疮（SLE）。另外合成了两种基于人单克隆抗DNA、16/6 Id的肽。进行这项研究是为了调查基于CDR的肽对SLE患者外周血淋巴细胞（PBL）的SLE相关反应进行免疫调节的能力。在62名接受检测的SLE患者中，有24名患者的PBL在用人16/6 Id刺激后在体外发生增殖。基于人和小鼠抗DNA自身抗体CDR的肽有效且特异性地抑制了16/6 Id诱导的增殖和IL-2产生。后者的抑制作用与免疫抑制细胞因子TGF-β的产生上调（2.5至3.5倍）相关。总体而言，我们的研究结果表明，基于CDR的肽能够在体外下调SLE患者PBL的自身反应性T细胞反应。因此，这些肽是SLE患者新型特异性治疗的潜在候选物。
