       Document 0227
 DOCN  M9620227
 TI    Effects of TH1 and TH2 cytokines on CD8+ cell response against human
       immunodeficiency virus: implications for long-term survival.
 DT    9602
 AU    Barker E; Mackewicz CE; Levy JA; Cancer Research Institute, University
       of California, San; Francisco 94143-0128, USA.
 SO    Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11135-9. Unique Identifier
       : AIDSLINE MED/96074662
 AB    CD8+ cells from long-term survivors [LTS; infected with human
       immunodeficiency virus (HIV) for 10 or more years and having CD4+ cell
       counts of > or = 500 cells per microliters] have a 3-fold greater
       ability to suppress HIV replication than do CD8+ cells from patients who
       have progressed to disease (progressors) during the same time period. A
       change in the pattern of cytokines produced in the host from those that
       typically favor cell-mediated immunity (T helper 1, TH1 or type 1) to
       those that down-regulate it (T helper 2, TH2 or type 2) was investigated
       as a cause of this reduced CD8+ cell anti-HIV function. Treatment of
       CD8+ cells from LTS with the TH1 cytokine interleukin (IL)-2 enhanced
       their anti-HIV activity, whereas exposure of these cells to TH2
       cytokines IL-4 or IL-10 reduced their ability to suppress HIV
       replication and to produce IL-2. IL-2 could prevent and reverse the
       inhibitory effects of IL-4 and IL-10. Moreover, prolonged exposure of
       CD8+ cells from some progressors to IL-2 improved the ability of these
       cells to suppress HIV replication. These observations support previous
       findings suggesting that strong CD8+ cell responses play an important
       role in maintaining an asymptomatic state in HIV infection. The data
       suggest that the loss of CD8+ cell suppression of HIV replication
       associated with disease progression results from a shift in cytokine
       production within the infected host from a TH1 to a TH2 pattern.
       Modulation of these cytokines could provide benefit to HIV-infected
       individuals by improving their CD8+ cell anti-HIV activity.
 DE    Cells, Cultured  Cytokines/*PHYSIOLOGY  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  CD8-Positive T-Lymphocytes/*IMMUNOLOGY
       Disease Progression  Human  HIV Infections/*IMMUNOLOGY  HIV-1/GROWTH &
       DEVELOPMENT/*IMMUNOLOGY  Immunity, Cellular  Interleukin-10/PHYSIOLOGY
       Interleukin-2/BIOSYNTHESIS  Interleukin-4/PHYSIOLOGY  Support, U.S.
       Gov't, P.H.S.  Th1 Cells/*PHYSIOLOGY  Th2 Cells/*PHYSIOLOGY  Time
       Factors  Virus Replication  JOURNAL ARTICLE

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

