       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).

