       Document 0394
 DOCN  M9620394
 TI    Contact of human immunodeficiency virus type 1-infected and uninfected
       CD4+ T lymphocytes is highly cytolytic for both cells.
 DT    9602
 AU    Heinkelein M; Sopper S; Jassoy C; Institute for Virology and
       Immunobiology, Wurzburg University,; Germany.
 SO    J Virol. 1995 Nov;69(11):6925-31. Unique Identifier : AIDSLINE
       MED/96013793
 AB    Individuals infected with the human immunodeficiency virus (HIV)
       experience a marked loss of CD4+ T lymphocytes, leading to fatal
       immunodeficiency. The mechanisms causing the depletion of these cells
       are not yet understood. In this study, we observed that CD4+ T
       lymphocytes from HIV type 1 (HIV-1)-infected and uninfected individuals
       rapidly lysed B lymphoblasts expressing the HIV-1 envelope glycoprotein
       on the cell surface and Jurkat cells expressing the complete virus.
       Contact of uninfected CD4+ T cells with envelope glycoprotein-expressing
       cells also resulted in the lysis of the uninfected CD4+ T cells.
       Cytolysis did not require priming or in vitro stimulation of the CD4+ T
       cells and was not restricted by major histocompatibility complex
       molecules. Cytotoxicity was inhibited by soluble CD4 and anti-CD4
       monoclonal antibodies that block binding of CD4 to gp120. In addition,
       neutralizing anti-CD4 and anti-gp120 monoclonal antibodies which block
       postbinding membrane fusion events and syncytium formation also
       inhibited cell lysis, suggesting that identical mechanisms in
       HIV-infected cultures underlie cell-cell fusion and the cytolysis
       observed. However, cytotoxicity was not always accompanied by the
       formation of visible syncytia. Rapid cell lysis after contact of
       uninfected and HIV-1-infected CD4+ T cells may explain CD4+ T-cell
       depletion in the absence of detectable syncytia in infected individuals.
       Moreover, because of its vigor, lysis of envelope-expressing targets by
       contact with unprimed CD4+ T lymphocytes may at first glance resemble
       antigen-specific immune responses and should be excluded when cytotoxic
       T-lymphocyte responses in infected individuals and vaccinees are
       evaluated.
 DE    Antibodies, Blocking/PHARMACOLOGY  Antibodies, Monoclonal/PHARMACOLOGY
       Antigens, CD/IMMUNOLOGY  Antigens, CD4/IMMUNOLOGY  *Cell Communication
       Cell Line  Comparative Study  *Cytotoxicity, Immunologic  CD4-Positive
       T-Lymphocytes/*IMMUNOLOGY/*VIROLOGY  CD8-Positive
       T-Lymphocytes/IMMUNOLOGY  Giant Cells  Human  HIV Envelope Protein
       gp120/IMMUNOLOGY  HIV Infections/BLOOD/*IMMUNOLOGY  HIV-1/*IMMUNOLOGY
       Immunophenotyping  Major Histocompatibility Complex  Reference Values
       Support, Non-U.S. Gov't  T-Lymphocytes/IMMUNOLOGY  JOURNAL ARTICLE

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

