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M9620394.TXT
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1996-02-26
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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).