Document 0266
 DOCN  M94A0266
 TI    Studies of the mechanism of cytolysis by HIV-1-specific CD4+ human CTL
       clones induced by candidate AIDS vaccines.
 DT    9412
 AU    Miskovsky EP; Liu AY; Pavlat W; Viveen R; Stanhope PE; Finzi D; Fox WM
       3rd; Hruban RH; Podack ER; Siliciano RF; Department of Medicine, Johns
       Hopkins University School of; Medicine, Baltimore, MD 21205.
 SO    J Immunol. 1994 Sep 15;153(6):2787-99. Unique Identifier : AIDSLINE
       MED/94358445
 AB    Vaccine-induced, virus-specific CTLs may rapidly eliminate the host
       cells that first become infected after virus exposure, thereby
       preventing disseminated infection. Thus, there is much interest in the
       ability of candidate AIDS vaccines to elicit CTLs. All HIV-1 envelope
       (env) protein-based vaccines tested to date in seronegative humans
       induce CTLs from the CD4+ subset. Because the mechanism of cytolysis by
       CD4+ CTLs is controversial, a detailed study of the cytolytic reactions
       mediated by vaccine-induced, HIV-1-specific human CD4+ CTL clones was
       conducted. CD4+ CTL clones induced rapid destruction of Ag-pulsed target
       cells. Lysis was readily detectable within 15 min. Lysis was not a
       result of syncytium formation between CD4+ effector cells and
       env-expressing targets. Target cell destruction was not dependent upon
       de novo RNA or protein synthesis in either the effector or the target
       cell. Expression of perforin mRNA was detected by Northern blotting and
       reverse-transcriptase-PCR in CD4+ CTL clones but not in autologous B
       lymphoblastoid cell lines. Immunohistochemical studies demonstrated
       perforin protein in cytoplasmic granules in CD4+ CTL clones. Lysis by
       CD4+ CTLs was strictly dependent upon extracellular Ca2+ and was highly
       specific, with no lysis of innocent bystander cells. DNA fragmentation
       was detectable in target cells, but did not precede 51Cr release. Taken
       together, these results provide a dramatically different view of
       cytolysis by human CD4+ CTLs. Target cells are lysed by a rapid and
       efficient mechanism that involves a preformed mediator and that is
       functionally similar to the mechanism used by CD8+ CTLs.
 DE    Apoptosis/IMMUNOLOGY  AIDS Vaccines/*IMMUNOLOGY  Base Sequence
       Calcium/PHYSIOLOGY  Cell Line  Clone Cells  Cytotoxicity Tests,
       Immunologic  Gene Products, env/IMMUNOLOGY  Giant Cells/IMMUNOLOGY
       Human  HIV-1/*IMMUNOLOGY  Immunohistochemistry  Membrane
       Glycoproteins/BIOSYNTHESIS  Molecular Sequence Data  Polymerase Chain
       Reaction  Protein Precursors/IMMUNOLOGY  Support, U.S. Gov't, P.H.S.
       T-Lymphocytes, Cytotoxic/*IMMUNOLOGY  T4 Lymphocytes/*IMMUNOLOGY
       JOURNAL ARTICLE

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