       Document 0117
 DOCN  M9630117
 TI    Upregulation of Fas ligand expression by human immunodeficiency virus in
       human macrophages mediates apoptosis of uninfected T lymphocytes.
 DT    9603
 AU    Badley AD; McElhinny JA; Leibson PJ; Lynch DH; Alderson MR; Paya CV;
       Department of Immunology, Mayo Clinic, Rochester, Minnesota; 55905, USA.
 SO    J Virol. 1996 Jan;70(1):199-206. Unique Identifier : AIDSLINE
       MED/96099431
 AB    Apoptosis has been proposed to mediate CD4+ T-cell depletion in human
       immunodeficiency virus (HIV)-infected individuals. Interaction of Fas
       ligand (FasL) with Fas (CD95) results in lymphocyte apoptosis, and
       increased susceptibility to Fas-mediated apoptosis has been demonstrated
       in lymphocytes from HIV-infected individuals. Cells undergoing apoptosis
       in lymph nodes from HIV-infected individuals do not harbor virus, and
       therefore a bystander effect has been postulated to mediate apoptosis of
       uninfected cells. These data raise the possibility that
       antigen-presenting cells are a source of FasL and that HIV infection of
       cells such as macrophages may induce or increase FasL expression. In
       this report, we demonstrate that HIV infection of monocytic cells not
       only increases the surface expression of Fas but also results in the de
       novo expression of FasL. Interference with the FasL-Fas interaction by
       anti-Fas blocking antibodies abrogates HIV-induced apoptosis of
       monocytic cells. Human monocyte-derived macrophages from healthy donors
       contain detectable FasL mRNA, which is further upregulated following HIV
       infection with monocytotropic strains. HIV-infected human macrophages
       result in the apoptotic death of Jurkat T cells and peripheral blood T
       lymphocytes. Interruption of the FasL-Fas interaction abrogates the
       HIV-infected macrophage-dependent death of T lymphocytes. These results
       provide evidence that human macrophages can provide a source of FasL,
       especially following HIV infection, and can thus participate in
       lymphocyte depletion in HIV-infected individuals.
 DE    Antigens, CD95/METABOLISM  *Apoptosis  Cell Line  Human
       HIV-1/*PHYSIOLOGY  Lymphocyte Depletion
       Macrophages/*METABOLISM/VIROLOGY  Membrane Glycoproteins/*METABOLISM
       T-Lymphocytes/*PHYSIOLOGY  Tumor Cells, Cultured  Up-Regulation
       (Physiology)  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

