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1996-02-26
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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).