Targeting HIV‐1 to FcγR on human phagocytes via bispecific antibodies reduces infectivity of HIV‐1 to T cells

In addition to CD4, the primary receptor to which the human immunodeficiency virus type 1 (HIV‐1) binds, mononuclear phagocytes (monocytes) express three classes of Fc receptors for immunoglobulin G (FcγR). We have previously shown that infection of monocytes by HIV‐1 is inhibited when bispecific antibodies (BsAbs) are used to target the virus to either the type I, type II, or type III FcγR on these cells. Infection of monocytes was not inhibited when HIV‐1 was targeted to either human leukocyte antigen class I or CD33. We have extended these studies to examine the ability of BsAbs plus polymorphonuclear leukocytes (neutrophils, PMNs) and monocytes to reduce infectivity of HIV‐1 to cells from the human T cell lymphoma line, H9. The production of HIV‐1 following interaction of virus with BsAb and phagocytes was determined in an indicator cell assay by mixing BsAb, HIV‐1, and phagocytes with uninfected H9 cells. Productive infection of H9 cells was quantitated on subsequent days by measuring p24 gag antigen levels in supernatants by enzyme‐linked immunosorbent assay. Our findings show that the addition of interferon‐γ‐activated PMNs or monocytes to cultures of HIV‐1 plus H9 cells in the absence of BsAb results in a marked reduction in p24 levels equivalent to 85 to 90% of control levels. With the combination of BsAb (anti‐FcγRI anti‐gpl20) plus IFN‐γ‐activated phagocytes, levels of p24 in H9 cultures were below those at culture initiation. These findings demonstrate that IFN‐γ‐activated phagocytes can affect the natural course of HIV‐1 infection of T cells, a finding of potential clinical importance. J. Leukoc . Biol . 55: 385–391; 1994.