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1996-02-27
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Document 0341
DOCN M9630341
TI T helper type 1/T helper type 2 cytokines and T cell death: preventive
effect of interleukin 12 on activation-induced and CD95
(FAS/APO-1)-mediated apoptosis of CD4+ T cells from human
immunodeficiency virus-infected persons.
DT 9603
AU Estaquier J; Idziorek T; Zou W; Emilie D; Farber CM; Bourez JM; Ameisen
JC; Institut National de la Sante et de la Recherche Medicale; (INSERM)
U 415, Institut Pasteur, Lille, France.
SO J Exp Med. 1995 Dec 1;182(6):1759-67. Unique Identifier : AIDSLINE
MED/96096449
AB Human immunodeficiency virus (HIV) infection leads to a progressive loss
of CD4+ T helper (Th) type 1 cell-mediated immunity that is associated
with defective in vitro CD4+ T cell proliferation and abnormal T cell
death by apoptosis in response to T cell receptor (TCR) stimulation.
Quantification of interleukin (IL)-2, interferon gamma, IL-4, IL-5, and
IL-10 secretion by immunoassays, and of interferon gamma, IL-4 and IL-10
messenger RNA expression by competitive reverse transcriptase polymerase
chain reaction after in vitro stimulation of the TCR revealed a similar
Th1 cytokine profile in T cells from HIV-infected persons and from
controls. These data indicated that the loss of CD4+ Th1 cell function
in HIV-infected persons is not related to a Th1 to Th2 cytokine switch
as previously proposed, but to a process of activation-induced death of
CD4+ Th1 cells. Despite the absence of elevated levels of Th2 cytokines,
apoptosis of CD4+ T cells, but not of CD8+ T cells, was prevented in
vitro by antibodies to IL-10 or IL-4, two Th2 cytokines that
downregulate Th1 cell responses, or by the addition of recombinant
IL-12, a cytokine that upregulates Th1 functions. TCR-induced apoptosis
of T cell hybridomas and preactivated T cells has been shown to involve
the CD95 (Fas/Apo-1) molecule. CD4+ and CD8+ T cells from HIV-infected
persons expressed high levels of the CD95 molecule, and, in contrast to
T cells from controls, were highly sensitive to antibody-mediated CD95
ligation, which induced apoptosis in a percentage of T cells similar to
that induced by TCR stimulation. As TCR-induced apoptosis, CD95-mediated
apoptosis of CD4+ T cells, but not of CD8+ T cells, was prevented by the
addition of recombinant IL-12. Together, these findings suggest that
apoptosis of CD4+ T cells from HIV-infected persons involves an abnormal
sensitivity to CD95 ligation, and to TCR stimulation in the presence of
normal levels of Th2 cytokines. The preventive effect of IL-12 on both
mechanisms has potential implications for the design of immunotherapy
strategies aimed at the upregulation of CD4+ Th1 cell functions in AIDS.
DE Antigens, CD95/*PHYSIOLOGY Apoptosis/*DRUG EFFECTS Base Sequence
Cells, Cultured Cytokines/*PHARMACOLOGY CD8-Positive
T-Lymphocytes/IMMUNOLOGY DNA Primers/CHEMISTRY Gene Expression Human
HIV Infections/*IMMUNOLOGY Interleukin-10/PHYSIOLOGY
Interleukin-12/*PHARMACOLOGY Interleukin-4/PHYSIOLOGY *Lymphocyte
Transformation Molecular Sequence Data RNA, Messenger/GENETICS
Support, Non-U.S. Gov't Th1 Cells/*IMMUNOLOGY Th2 Cells/*IMMUNOLOGY
JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).