Watanabe M, Levine C G, Shen L, Fisher R A, Letvin N L
Harvard Medical School, New England Regional Primate Research Center, Southborough, MA 01772.
Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4616-20. doi: 10.1073/pnas.88.11.4616.
Since the CD4 molecule is a high-affinity cell-surface receptor for the human immunodeficiency virus (HIV), it has been suggested that a soluble truncated form of CD4 may compete with cell-surface CD4 for HIV binding and thus be of use in the therapy of AIDS. We have utilized the simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys to explore another possible therapeutic application of CD4 in AIDS--the use of recombinant soluble CD4 (rsCD4) as an immunogen. SIVmac-infected rhesus monkeys immunized with human rsCD4 developed not only an anti-human CD4 but also an anti-rhesus monkey CD4 antibody response. Coincident with the generation of this antibody response, SIVmac could not be isolated easily from peripheral blood lymphocytes and bone marrow macrophages of these animals. Furthermore, the decreased number of both granulocyte/macrophage and erythrocyte colonies grown from the bone marrow of these immunized monkeys rose to normal levels. These findings suggest that a modified human CD4 molecule serving as an immunogen might elicit an antibody response in man that could induce a beneficial therapeutic response in HIV-infected individuals.
由于CD4分子是人类免疫缺陷病毒（HIV）的高亲和力细胞表面受体，因此有人提出，可溶性截短形式的CD4可能会与细胞表面的CD4竞争HIV结合，从而可用于治疗艾滋病。我们利用感染了猕猴猿免疫缺陷病毒（SIVmac）的恒河猴来探索CD4在艾滋病治疗中的另一种可能的应用——使用重组可溶性CD4（rsCD4）作为免疫原。用人类rsCD4免疫感染SIVmac的恒河猴，不仅产生了抗人类CD4抗体反应，还产生了抗恒河猴CD4抗体反应。与这种抗体反应的产生同时发生的是，在这些动物的外周血淋巴细胞和骨髓巨噬细胞中不容易分离出SIVmac。此外，从这些免疫猴子的骨髓中生长的粒细胞/巨噬细胞集落和红细胞集落数量减少的情况恢复到了正常水平。这些发现表明，作为免疫原的修饰人类CD4分子可能会在人体内引发抗体反应，从而可能在HIV感染个体中诱导有益的治疗反应。
