Wu X, Okada N, Momota H, Irie R F, Okada H
Department of Molecular Biology, Nagoya City University School of Medicine, Japan.
J Immunol. 1999 Jan 1;162(1):533-9.
HIV-infected cells aberrantly express a high level of antigenic glycosidic structures such as GM2 and Gg4. Some normal sera containing natural IgM Abs to GM2 and/or Gg4 cause C-mediated cytolysis of HIV-infected cells. In the present study we demonstrated that a human IgM anti-GM2 mAb (L55 Ab) can induce cytolysis of HIV-infected cells. Increased GM2 expression by HIV-1 infection of a human T cell line (MOLT4), a human monocyte cell line (U937), and human lymphoblastoid cells was confirmed by immunofluorescence staining with L55 Ab. These infected cells were readily lysed by L55 Ab in the presence of fresh human serum as a C source that alone did not cause cytolysis. L55 Ab also had the ability to destroy HIV-1 particles via C-mediated lysis. By adding L55 Ab together with human C to mixed culture of HIV-infected cells and naive cells, HIV-1 replication was significantly suppressed, and this effect was synergistic when L55 Ab was combined with a reverse transcriptase inhibitor and a proteinase inhibitor. Therefore, a human IgM anti-GM2 mAb may be effective in treating HIV-infected patients, especially when used together with chemotherapeutic agents.
感染HIV的细胞异常表达高水平的抗原性糖苷结构,如GM2和Gg4。一些含有天然抗GM2和/或Gg4 IgM抗体的正常血清可引起补体介导的HIV感染细胞的细胞溶解。在本研究中,我们证明了一种人源抗GM2 IgM单克隆抗体(L55抗体)可诱导HIV感染细胞的细胞溶解。通过用L55抗体进行免疫荧光染色,证实了HIV-1感染人T细胞系(MOLT4)、人单核细胞系(U937)和人淋巴母细胞后GM2表达增加。在作为补体来源的新鲜人血清存在下,这些感染细胞很容易被L55抗体裂解,而单独的新鲜人血清不会引起细胞溶解。L55抗体还具有通过补体介导的裂解作用破坏HIV-1颗粒的能力。通过将L55抗体与人补体一起添加到HIV感染细胞和未感染细胞的混合培养物中,HIV-1复制受到显著抑制,当L55抗体与逆转录酶抑制剂和蛋白酶抑制剂联合使用时,这种效果具有协同作用。因此,人源抗GM2 IgM单克隆抗体可能对治疗HIV感染患者有效,尤其是与化疗药物联合使用时。