Granulocyte- and granulocyte-macrophage colony-stimulating factors enhance neutrophil cytotoxicity toward HIV-infected cells

Abstract

Although the control of retroviral disease in animal systems often involves antibody-dependent cell-mediated cytotoxicity (ADCC), the role of cytotoxic function in human retroviral disorders is uncertain. The ability of the neutrophil to kill HIV-infected targets directed by antiviral antibody was examined. Neutrophils from patients with AIDS killed HIV-infected MOLT-3A cells in a manner equivalent to neutrophils obtained from normal volunteers. Both granulocyte- and granulocyte-macrophage colony-stimulating factors (G-CSF and GM-CSF) markedly augmented the cytotoxic function. Studies done with fractionated human antisera revealed that ADCC to HIV-infected cells was mediated only by antibody to the env glycoprotein. ADCC in this system was not dependent on oxidative metabolism because neutrophils from patients with chronic granulomatous disease (CGD) were capable of CSF-augmented cytotoxicity. Although ADCC can be mediated by various classes of lymphocytes and mononuclear phagocytes, such cells may be infected by HIV. Because the neutrophil apparently is not productively infected by the virus, it is an ideal cell to focus on with regard to cytotoxic function in AIDS patients. The findings regarding neutrophil ADCC in AIDS are clinically relevant because the availability of CSFs now permits therapeutic regulation of neutrophils in AIDS patients, and presumably natural antibody may be useful in targeting HIV-infected cells for neutrophil cytotoxicity in vivo.