Document 0247
 DOCN  M95A0247
 TI    Adhesion co-receptor expression and intracellular signalling in HIV
       disease: implications for immunotherapy.
 DT    9510
 AU    Ng TT; Guntermann C; Nye KE; Parkin JM; Anderson J; Norman JE; Morrow
       WJ; Department of Immunology, St Bartholomew's Hospital, London, UK.
 SO    AIDS. 1995 Apr;9(4):337-43. Unique Identifier : AIDSLINE MED/95314788
 AB    OBJECTIVES: To investigate, in lymphocytes from HIV-1-infected
       individuals, the phenotypic expression of various adhesion co- or
       counter-receptors [lymphocyte function-associated antigen (LFA)-3, LFA-1
       and intercellular adhesion molecule (ICAM)-1] involved in providing the
       co-stimulatory signal through the phospholipase C-gamma pathway in
       relation to inositol polyphosphate metabolism. DESIGN AND METHODS: Cell
       adhesion molecule profiles of peripheral blood lymphocytes (PBL) from 39
       HIV-1-infected individuals at various stages of infection and 20 healthy
       laboratory controls were studied using flow cytometry. These were
       studied in 14 patients with late-stage disease in conjunction with their
       inositol polyphosphate metabolic profiles measured by high performance
       liquid chromatography. Levels of HIV-1 present in cell lysates were
       concurrently measured by a p24 antigen capture assay. In addition, the
       effects of a specific anti-ICAM-1 antisense oligonucleotide on the
       intracellular phosphatase activities of lymphocytes from a separate
       group of eight HIV-1-infected individuals were examined. RESULTS: The
       expression of LFA-1, a beta 2 integrin, was upregulated among patient
       PBL in parallel with disease progression, whereas that of LFA-3 (CD58)
       was found to be significantly reduced among the CD4+ lymphocyte subset
       in all stages of infection. The 5-phosphatase activity, which we
       previously observed to be defective in HIV disease, was found to
       correlate linearly with the expression of both LFA-1 and its ligand,
       ICAM-1. Treatment of patient lymphocytes with an antisense
       oligonucleotide, which reduced the cell surface expression of ICAM-1 by
       blocking the translation of its mRNA, resulted in further reduction of
       intracellular phosphatase activities. CONCLUSIONS: Our results suggest a
       pivotal role for adhesion co- and counter-receptors in influencing
       lymphocyte signalling and hence cellular response to recall antigens in
       HIV-1-infected individuals.
 DE    Antigens, CD/METABOLISM  Base Sequence  Cell Adhesion
       Molecules/*METABOLISM  Human  HIV
       Infections/*IMMUNOLOGY/METABOLISM/*THERAPY  *HIV-1  Immunotherapy  In
       Vitro  Inositol Phosphates/METABOLISM  Intercellular Adhesion
       Molecule-1/GENETICS/METABOLISM  Lymphocyte Function-Associated
       Antigen-1/METABOLISM  Lymphocytes/DRUG EFFECTS/IMMUNOLOGY/METABOLISM
       Male  Membrane Glycoproteins/METABOLISM  Molecular Sequence Data
       Oligonucleotides, Antisense/GENETICS/PHARMACOLOGY  Phosphoric Monoester
       Hydrolases/METABOLISM  Signal Transduction  Support, Non-U.S. Gov't
       JOURNAL ARTICLE

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