       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).

