de Kozak Y
Laboratoire d'Immunopathologie de l'Oeil, INSERM U86, Centre de recherche des Cordeliers, Paris, France.
Curr Eye Res. 1990;9 Suppl:193-200. doi: 10.3109/02713689008999441.
The immune response to self antigens is regulated through an interplay of idiotypes and anti-idiotypes expressed on antibodies and lymphoid cells. The equilibrium of the different components of the immune system has been modulated in various autoimmune diseases by manipulation of the idiotypic network. Experimental autoimmune uveoretinitis (EAU) was induced in rats with one foot pad injection of S-antigen (S-Ag) in complete Freund's adjuvant (CFA). 1. Injection of rats with the mouse anti-S-Ag monoclonal antibody (mAb) S2D2 either simultaneously with or before S-Ag challenge, led to an anti-idiotypic (anti-Id) response and to inhibition of EAU. 2. Suppression of the disease could be passively transferred using lymph node and/or spleen cells from donors immunized with S2D2 to naive recipients, prior to immunization with bovine S-Ag in CFA. In contrast, one injection of IgG from S2D2-immunized rats did not prevent EAU. 3. Preimmunization against a purified rat polyclonal anti-Id-S2D2 antibody (internal image of the epitope recognized by mAb S2D2) before S-Ag challenge also allowed to inhibit EAU. As S2D2 was the best of several anti-S-Ag mAbs tested for disease inhibition, the epitope recognized by S2D2 should be of particular interest in the regulation of the immune response. This epitope has been localized to the N-terminal region of S-Ag, in the amino acid sequence 40-50. The S2D2 epitope is distant from all presently known uveitogenic sites. Manipulation of the idiotypic network for selected epitopes of the autoantigen may provide a valuable approach to therapy of autoimmune disease.
针对自身抗原的免疫反应是通过抗体和淋巴细胞上表达的独特型和抗独特型之间的相互作用来调节的。在各种自身免疫性疾病中，通过操纵独特型网络调节了免疫系统不同组分的平衡。通过在弗氏完全佐剂（CFA）中向大鼠的一个足垫注射S抗原（S-Ag）诱导实验性自身免疫性葡萄膜视网膜炎（EAU）。1. 在S-Ag攻击同时或之前给大鼠注射小鼠抗S-Ag单克隆抗体（mAb）S2D2，可导致抗独特型（抗Id）反应并抑制EAU。2. 在用CFA中的牛S-Ag免疫之前，可使用来自用S2D2免疫的供体的淋巴结和/或脾细胞将疾病抑制被动转移至未免疫的受体。相比之下，注射来自S2D2免疫大鼠的IgG并不能预防EAU。3. 在S-Ag攻击之前针对纯化的大鼠多克隆抗Id-S2D2抗体（mAb S2D2识别的表位的内影像）进行预免疫也可抑制EAU。由于S2D2是所测试的几种用于疾病抑制的抗S-Ag mAb中效果最好的，S2D2识别的表位在免疫反应调节中应特别受关注。该表位已定位到S-Ag的N端区域，氨基酸序列为40-50。S2D2表位与所有目前已知的葡萄膜炎致病位点距离较远。操纵自身抗原选定表位的独特型网络可能为自身免疫性疾病的治疗提供一种有价值的方法。
