Levine B L, Mosca J D, Riley J L, Carroll R G, Vahey M T, Jagodzinski L L, Wagner K F, Mayers D L, Burke D S, Weislow O S, St Louis D C, June C H
Naval Medical Research Institute, Bethesda, Maryland 20889, USA.
Science. 1996 Jun 28;272(5270):1939-43. doi: 10.1126/science.272.5270.1939.
Because stimulation of CD4+ lymphocytes leads to activation of human immunodeficiency virus-type 1 (HIV-1) replication, viral spread, and cell death, adoptive CD4+ T cell therapy has not been possible. When antigen and CD28 receptors on cultured T cells were stimulated by monoclonal antibodies (mAbs) to CD3 and CD28 that had been immobilized, there was an increase in the number of polyclonal CD4+ T cells from HIV-infected donors. Activated cells predominantly secreted cytokines associated with T helper cell type 1 function. The HIV-1 viral load declined in the absence of antiretroviral agents. Moreover, CD28 stimulation of CD4+ T cells from uninfected donors rendered these cells highly resistant to HIV-1 infection. Immobilization of CD28 mAb was crucial to the development of HIV resistance, as cells stimulated with soluble CD28 mAb were highly susceptible to HIV infection. The CD28-mediated antiviral effect occurred early in the viral life cycle, before HIV-1 DNA integration. These data may facilitate immune reconstitution and gene therapy approaches in persons with HIV infection.
由于刺激CD4 +淋巴细胞会导致1型人类免疫缺陷病毒（HIV-1）复制、病毒传播和细胞死亡，因此过继性CD4 + T细胞疗法一直无法实现。当通过固定化的抗CD3和抗CD28单克隆抗体（mAb）刺激培养的T细胞上的抗原和CD28受体时，来自HIV感染供体的多克隆CD4 + T细胞数量增加。活化细胞主要分泌与1型辅助性T细胞功能相关的细胞因子。在没有抗逆转录病毒药物的情况下，HIV-1病毒载量下降。此外，用未感染供体的CD抗原刺激CD4 + T细胞可使这些细胞对HIV-1感染具有高度抗性。固定化CD28单克隆抗体对于HIV抗性的发展至关重要，因为用可溶性CD28单克隆抗体刺激的细胞对HIV感染高度敏感。CD28介导的抗病毒作用发生在病毒生命周期的早期，在HIV-1 DNA整合之前。这些数据可能有助于HIV感染者的免疫重建和基因治疗方法。
