Perosa F, Scudeletti M, Imro M A, Dammacco F, Indiveri F
Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari Medical School, Italy.
J Immunol. 1996 May 1;156(9):3563-9.
We previously showed that anti-idiotypic mAb (mAb2) F16-16D7 (16D7) to the paratope (or paratope-related idiotope) of the anti-CD4 mAb HP2/6 induces anti-CD4 Abs in BALB/c mice. In view of the potential ability of 16D7 to induce anti-CD4 Ab in humans and the potential benefits of anti-CD4 Abs in the treatment of autoimmune diseases, we evaluated the immunologic response to and assessed the safety of four 2-mg 16D7 s.c. injections in one patient with systemic lupus erythematosus (SLE) and one with rheumatoid arthritis (RA). 16D7 induced anti-isotypic and anti-anti-idiotypic Abs (Ab3), which were almost exclusively of the IgG isotype. Ab3 specifically reacted with 16D7 as they inhibited its binding to mAb HP2/6. Although Ab3 did not react with cellular or recombinant CD4 (rCD4), single-cell enzyme-linked immunospot assays of anti-CD4 Ab production revealed many more spot-forming cells in rCD4- and 16D7-coated wells than in wells coated with BSA or 16D7 isotype-matched MK2-23. Spot-forming anti-CD4 Abs were specifically induced by 16D7, since rCD4-dependent spot formation 1) was not observed with PBL from one patient with SLE, one with mixed connective tissue disease, and one with melanoma immunized with MK2-23; and 2) was inhibited by 16D7 and not by MK2-23. Spot-forming anti-CD4 Abs recognize a CD4 epitope identical (or closely related) to that seen by HP2/6, since this specifically inhibited spot formation. A substantial, although transient, CD4+ T cell depletion was only observed in the RA patient. Local and/or general toxicity and laboratory and/or clinical signs indicative of immunodepression or diseases relapse were not observed during an 18-month follow-up.
我们之前发现，针对抗CD4单克隆抗体HP2/6互补决定区（或与互补决定区相关的独特型表位）的抗独特型单克隆抗体（单克隆抗体2）F16-16D7（16D7）可在BALB/c小鼠中诱导产生抗CD4抗体。鉴于16D7在人体内诱导抗CD4抗体的潜在能力以及抗CD4抗体在自身免疫性疾病治疗中的潜在益处，我们评估了一名系统性红斑狼疮（SLE）患者和一名类风湿关节炎（RA）患者皮下注射4次2mg 16D7后的免疫反应并评估了其安全性。16D7诱导产生了抗同种型和抗抗独特型抗体（抗体3），这些抗体几乎均为IgG同种型。抗体3可与16D7特异性反应，因为它们可抑制16D7与单克隆抗体HP2/6的结合。尽管抗体3不与细胞或重组CD4（rCD4）反应，但抗CD4抗体产生的单细胞酶联免疫斑点试验显示，与用牛血清白蛋白（BSA）或16D7同种型匹配的MK2-23包被的孔相比，用rCD4和16D7包被的孔中形成斑点的细胞更多。形成斑点的抗CD4抗体是由16D7特异性诱导产生的，因为：1）在用MK2-23免疫的一名SLE患者、一名混合性结缔组织病患者和一名黑色素瘤患者的外周血淋巴细胞（PBL）中未观察到rCD4依赖性斑点形成；2）斑点形成受到16D7的抑制，而未受到MK2-23的抑制。形成斑点的抗CD4抗体识别的CD4表位与HP2/6识别的表位相同（或密切相关），因为这可特异性抑制斑点形成。仅在RA患者中观察到了显著但短暂的CD4+T细胞耗竭。在18个月的随访期间，未观察到局部和/或全身毒性以及表明免疫抑制或疾病复发的实验室和/或临床体征。
