Targeting HIV-1 to Fc gamma R 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 (Fc gamma R). 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 Fc gamma R 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-gamma-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-Fc gamma RI x anti-gp120) plus IFN-gamma-activated phagocytes, levels of p24 in H9 cultures were below those at culture initiation. These findings demonstrate that IFN-gamma-activated phagocytes can affect the natural course of HIV-1 infection of T cells, a finding of potential clinical importance.
Howell
A L
AL
Department of Medicine, Dartmouth Medical School, Lebanon, NH 03755-3842.
Guyre
P M
PM
You
K
K
Fanger
M W
MW
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000918:Antibody Specificity; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D015483:HIV Antibodies / Q000276:immunology* / Q000494:pharmacology; D016655:HIV Core Protein p24 / Q000032:analysis / Q000378:metabolism; D015497:HIV-1 / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000378:metabolism / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D009000:Monocytes / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D010586:Phagocytes / Q000737:chemistry* / Q000166:cytology* / Q000648:ultrastructure; D017452:Receptors, IgG / Q000032:analysis* / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000382:microbiology*
D015483:HIV Antibodies; D016655:HIV Core Protein p24; D007074:Immunoglobulin G; D017452:Receptors, IgG; D007371:Interferon-gamma