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M9610375.TXT
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1996-01-30
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Document 0375
DOCN M9610375
TI Cytokine interactions in human immunodeficiency virus-infected
individuals: roles of interleukin (IL)-2, IL-12, and IL-15.
DT 9601
AU Seder RA; Grabstein KH; Berzofsky JA; McDyer JF; National Institute of
Allergy and Infectious Diseases, National; Institutes of Health,
Bethesda, Maryland 20892, USA.
SO J Exp Med. 1995 Oct 1;182(4):1067-77. Unique Identifier : AIDSLINE
MED/96018806
AB Cytokines have been shown to be powerful regulators of the immune
response. In this study, we analyze the effect that the newly recognized
cytokine interleukin (IL)-15 has on proliferation and cytokine induction
using peripheral blood mononuclear cells (PBMCs) and purified CD4+ T
cells from patients infected with human immunodeficiency virus (HIV) who
are at various stages in their disease. We observed that IL-15 enhances
the proliferative response in a dose-dependent manner from PBMCs of
HIV-infected individuals when stimulated by polyclonal mitogen, tetanus
toxoid, or HIV-specific antigen. The effects of exogenous IL-15 are
substantially diminished by adding a neutralizing antibody to the beta
chain of the IL-2 receptor. Moreover, the ability of IL-15 to increase
proliferation is enhanced by the presence of endogenous IL-2 produced in
the cultures. The effect that exogenous IL-15 had on IL-2, IL-4, and
interferon (IFN)-gamma induction from PBMC's or CD4+ T cells in response
to mitogen or tetanus toxoid was also examined. This was compared to the
effect that exogenous IL-2 and IL-12 had under the same conditions.
Addition of IL-2 or IL-15 to short-term in vitro cultures of either
PBMCs or CD4+ T cells had little effect on IL-2, IL-4, or IFN-gamma
production. By contrast, IL-12 caused substantial enhancement of both
IL-2 and IFN-gamma production from these cultures. The role that
endogenous cytokines have on IFN-gamma induction was also studied.
Addition of a neutralizing antibody to the alpha chain of the IL-2
receptor or IL-12 to antigen stimulated cultures caused a striking
decrease in IFN-gamma production. Neutralization of endogenous IL-15
also resulted in diminished IFN-gamma production from cultures
stimulated with mitogen. IL-4 and IFN-gamma protein production by PBMCs
and CD4+ T cells stimulated with mitogen was assessed to see if we could
detect a specific bias of cytokine production. Small amounts of IL-4
were detected from CD4+ T cells but not PBMCs from most individuals
tested. IFN-gamma and IL-2, however, were also produced from these same
cultures. These results further elucidate the mechanism of cytokine
regulation in HIV-infected individuals, and they provide evidence that
IL-15 may be a useful immune modulator.
DE Comparative Study CD4-Positive T-Lymphocytes/IMMUNOLOGY Drug
Interactions Human HIV Antigens/PHARMACOLOGY HIV
Infections/*IMMUNOLOGY Interferon Type II/*BIOSYNTHESIS
Interleukin-12/PHARMACOLOGY Interleukin-2/BIOSYNTHESIS/PHARMACOLOGY
Interleukins/*PHARMACOLOGY Leukocytes, Mononuclear/*IMMUNOLOGY
Lymphocyte Transformation/*DRUG EFFECTS Mitogens/PHARMACOLOGY
Receptors, Interleukin-2/IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).