Hober D, Jewett A, Bonavida B
Department of Microbiology and Immunology, UCLA School of Medicine, University of California 90024, USA.
FEMS Immunol Med Microbiol. 1995 Jan;10(2):83-91. doi: 10.1111/j.1574-695X.1995.tb00015.x.
Previous reports from our laboratory have demonstrated that peripheral blood monocytes (PBM) from HIV-1 infected individuals are de novo activated and are cytotoxic in vitro. Significant monocyte-antibody-dependent cellular cytotoxicity (ADCC) was obtained against HIV-1 inactivated CD4+ CEM target cells coated with HIV-1 in the presence of autologous seropositive serum. Based on these findings, we hypothesized that in HIV-seropositive individuals the monocytes may play an important role in vivo in the autodestruction of non-infected CD4+ T lymphocytes. The present study was designed to test this hypothesis. Monocytes from normal donors activated with M-CSF lysed CD4+ T cells (CEM) coated with gp120 sensitized by plasma from asymptomatic HIV-1+ individuals in a 8 h 51Cr release assay. ADCC cytotoxic activity varied from one individual to another and was a function of the dilution of the individual seropositive plasma used. We then used circulating CD3+ T lymphocytes as targets for ADCC following treatment with actinomycin D to facilitate the release of radioactive 51Cr. Like CEM, ADCC was obtained with CD3+ T cells coated with gp120 in the presence of HIV seropositive plasma and monocytes. Lysis was specific as T cells that were not coated with gp120 were not destroyed. These findings demonstrate that activated peripheral blood derived monocytes can destroy non-infected gp120-coated circulating T lymphocytes by an ADCC-mediated mechanism. Thus, these findings suggest that ADCC may be one mechanism operating in vivo for the destruction of non-infected CD4+ T lymphocytes.
我们实验室之前的报告表明，来自HIV-1感染个体的外周血单核细胞（PBM）会被重新激活，并且在体外具有细胞毒性。在自体血清阳性血清存在的情况下，针对包被有HIV-1的HIV-1灭活CD4+CEM靶细胞，可获得显著的单核细胞抗体依赖性细胞毒性（ADCC）。基于这些发现，我们推测在HIV血清阳性个体中，单核细胞可能在体内对未感染的CD4+T淋巴细胞的自身破坏中发挥重要作用。本研究旨在验证这一假设。在8小时的51Cr释放试验中，用M-CSF激活的正常供体单核细胞裂解了由无症状HIV-1+个体血浆致敏的包被有gp120的CD4+T细胞（CEM）。ADCC细胞毒性活性因个体而异，并且是所用个体血清阳性血浆稀释度的函数。然后，在用放线菌素D处理后，我们将循环CD3+T淋巴细胞作为ADCC的靶标，以促进放射性51Cr的释放。与CEM一样，在HIV血清阳性血浆和单核细胞存在的情况下，包被有gp120的CD3+T细胞可产生ADCC。裂解具有特异性，因为未包被gp120的T细胞未被破坏。这些发现表明，活化的外周血来源单核细胞可通过ADCC介导的机制破坏未感染的包被有gp120的循环T淋巴细胞。因此，这些发现表明ADCC可能是体内破坏未感染的CD4+T淋巴细胞的一种作用机制。
