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M9620228.TXT
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1996-02-26
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Document 0228
DOCN M9620228
TI Interleukin 2 induces CD8+ T cell-mediated suppression of human
immunodeficiency virus replication in CD4+ T cells and this effect
overrides its ability to stimulate virus expression.
DT 9602
AU Kinter AL; Bende SM; Hardy EC; Jackson R; Fauci AS; Laboratory of
Immunoregulation, National Institute of Allergy and; Infectious
Diseases, National Institutes of Health, Bethesda, MD; 20892, USA.
SO Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):10985-9. Unique Identifier
: AIDSLINE MED/96074631
AB The nonlytic suppression of human immunodeficiency virus (HIV)
production from infected CD4+ T cells by CD8+ lymphocytes from
HIV-infected individuals is one of the most potent host-mediated
antiviral activities observed in vitro. We demonstrate that the
pleiotropic cytokine interleukin 2 (IL-2), but not IL-12, is a potent
inducer of the CD8+ HIV suppressor phenomenon. IL-2 induces HIV
expression in peripheral blood or lymph node mononuclear cells from
HIV-infected individuals in the absence of CD8+ T cells. However, IL-2
induces CD8+ T cells to suppress HIV expression when added back to these
cultures, and this effect dramatically supersedes the ability to IL-2 to
induce HIV expression. Five to 25 times fewer CD8+ cells were required
to obtain comparable levels of inhibition of viral production if they
were activated in the presence of IL-2 as compared with IL-12 or no
exogenous cytokine. Furthermore, IL-2 appeared either to induce a
qualitative increase in HIV suppressor cell activity or to increase the
relative frequency of suppressor cells in the activated (CD25+) CD8+
populations. Analyses of proviral levels in peripheral blood mononuclear
cells suggest that CD8+ T cell-mediated lysis of in vivo infected cells
is not induced by IL-2. These results have implications for our
understanding of the effects of impaired IL-2 production during HIV
disease as well as the overall effects of IL-2-based immunotherapy on
HIV replication in vivo.
DE CD4-Positive T-Lymphocytes/*MICROBIOLOGY CD8-Positive
T-Lymphocytes/*IMMUNOLOGY Human HIV Infections/*IMMUNOLOGY
HIV-1/*GROWTH & DEVELOPMENT Interleukin-12/PHYSIOLOGY
Interleukin-2/*PHYSIOLOGY Lymphocyte Transformation/DRUG EFFECTS
Receptors, Interleukin-2/ANALYSIS/PHYSIOLOGY T-Lymphocyte
Subsets/*IMMUNOLOGY T-Lymphocytes, Suppressor-Effector/*IMMUNOLOGY
*Virus Replication JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).