Granulocyte- and granulocyte-macrophage colony-stimulating factors enhance
neutrophil cytotoxicity toward HIV-infected cells
GC Baldwin, ND Fuller, RL Roberts, DD Ho and DW Golde
Division of Hematology-Oncology, UCLA School of Medicine.
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.
Volume 74,
Issue 5,
pp. 1673-1677,
10/01/1989
Copyright © 1989 by The American Society of Hematology
