Document 0583
 DOCN  M9460583
 TI    Targeting HIV-1 to Fc gamma R on human phagocytes via bispecific
       antibodies reduces infectivity of HIV-1 to T cells.
 DT    9404
 AU    Howell AL; Guyre PM; You K; Fanger MW; Department of Medicine, Dartmouth
       Medical School, Lebanon, NH; 03755-3842.
 SO    J Leukoc Biol. 1994 Mar;55(3):385-91. Unique Identifier : AIDSLINE
       MED/94165577
 AB    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.
 DE    Acquired Immunodeficiency Syndrome/IMMUNOLOGY  *Antibody Specificity
       Cells, Cultured  Enzyme-Linked Immunosorbent Assay  Fluorescent Antibody
       Technique  Human  HIV Antibodies/*IMMUNOLOGY/PHARMACOLOGY  HIV Core
       Protein p24/ANALYSIS/METABOLISM  HIV-1/ISOLATION &
       PURIF/*METABOLISM/*PHYSIOLOGY  IgG/METABOLISM/PHARMACOLOGY  Immunity,
       Natural  Interferon Type II/PHARMACOLOGY
       Monocytes/CHEMISTRY/CYTOLOGY/ULTRASTRUCTURE
       Neutrophils/CHEMISTRY/CYTOLOGY/ULTRASTRUCTURE
       Phagocytes/*CHEMISTRY/*CYTOLOGY/ULTRASTRUCTURE  Receptors,
       IgG/*ANALYSIS/METABOLISM  Support, Non-U.S. Gov't  Support, U.S. Gov't,
       Non-P.H.S.  Support, U.S. Gov't, P.H.S.
       T-Lymphocytes/*CYTOLOGY/*MICROBIOLOGY  JOURNAL ARTICLE

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