       Document 0088
 DOCN  M9610088
 TI    Mechanism of apoptosis in peripheral blood mononuclear cells of
       HIV-infected patients.
 DT    9601
 AU    Oyaizu N; McCloskey TW; Than S; Hu R; Pahwa S; Department of Pediatrics,
       North Shore University Hospital-Cornell; University Medical College,
       Manhasset, New York, New York 11030,; USA.
 SO    Adv Exp Med Biol. 1995;374:101-14. Unique Identifier : AIDSLINE
       MED/96047241
 AB    Lymphocytes from patients with HIV-infection have been shown to undergo
       accelerated spontaneous apoptosis. Binding of CD4 molecules by HIV
       envelope protein gp120 and anti-gp120 antibodies can lead to
       crosslinking of CD4 molecules (CD4XL) in vitro and conceivably in vivo.
       We have recently shown that CD4XL in vitro, when performed in
       unfractioned peripheral blood mononuclear cells (PBMC) on normal HIV
       seronegative donors, is by itself sufficient to induce T cell apoptosis
       (Blood 82:3392, 1993). To further examine the mechanisms involved in
       apoptosis, we have examined the expression of Fas antigen (Fas) using 3
       color flow cytometry. Fas is a cell surface molecule known to mediate
       apoptosis-triggering signals. We induced CD4XL in PBMC obtained from
       normal donors, either by anti-CD4 mAb Leu3a or by HIV-1 envelope protein
       gp160. PBMC subpopulations were examined for Fas Ag expression and for
       apoptosis induction by flow cytometry. CD4XL was found to result in
       increased Fas expression as well as Fas mRNA in lymphocytes and the
       up-regulated Fas Ag was closely correlated with apoptotic cell death.
       CD4XL in PBMC also resulted in induction of the cytokines INF-tau and
       TNF-alpha in the absence of IL-2 and IL-4 secretion. Both these cytokins
       contributed to Fas Ag up-regulation and antibodies to TNF-alpha and
       INF-tau abrogated CD4XL-induced Fas up-regulation and T-cell apoptosis.
       These findings suggest that CD4XL occurring in vivo might play an
       important role in inducing an abberant cytokine profile (which has been
       observed in HIV infected individuals) and also in triggering of T-cell
       apoptosis.
 DE    Antigens, CD4/BLOOD  Antigens, CD95/BIOSYNTHESIS  Apoptosis/*PHYSIOLOGY
       Cells, Cultured  Cross-Linking Reagents  Human  HIV
       Infections/BLOOD/*PATHOLOGY  Interferon Type I/SECRETION  Pregnancy
       Proteins/SECRETION  Support, U.S. Gov't, P.H.S.
       T-Lymphocytes/*PATHOLOGY  Tumor Necrosis Factor/SECRETION  Up-Regulation
       (Physiology)  JOURNAL ARTICLE

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

