Document 3227
 DOCN  M94A3227
 TI    HIV infection induces thymocyte depletion in the SCID-hu mouse.
 DT    9412
 AU    Kaneshima H; Bonyhadi M; Su L; Connor R; Ho D; McCune JM; SyStemix,
       Inc., Palo Alto, California 94304.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):124 (abstract no. PA0117). Unique
       Identifier : AIDSLINE ICA10/94369348
 AB    A variety of mechanisms have been proposed to account for the observed
       loss of CD4+ cells after HIV infection. However, little is known about
       the events which occur within infected lymphoid organs wherein most CD4
       T cells mature and function. To understand HIV pathogenesis in vivo, we
       have developed a SCID-hu mouse model in which engrafted human thymus
       supports stable and long-term human T lymphopoiesis. Recently, we have
       demonstrated that human thymopoiesis in the SCID-hu mouse is suppressed
       as a function of time after HIV infection, as measured by cell number,
       FACS profile, CD4/CD8 ratio and immunohistochemistry. The severe loss of
       CD4+ cells appears to be mediated at least in part by a process which is
       consistent with programmed cell death (apoptosis), as determined by
       electron microscopy and by the incorporation of dNTP with terminal
       deoxynucleotidyl transferase into the cells. Initial experiments
       indicated that the kinetics of thymocyte depletion in the SCID-hu mouse.
       We have now extended this analysis to include a series of HIV isolates
       obtained from individual patients at different times. Low levels of
       viral replication and minimal depletion were observed after infection
       with non syncytium-inducing (NSI) isolates obtained from patients with
       normal CD4 counts. In contrast, high levels of viral replication and T
       cell depletion were observed after infection with syncytium-inducing
       (SI) isolates obtained from the same patients after the CD4 count
       dropped. These observations indicate that the mechanism(s) of thymocyte
       depletion in the SCID-hu mouse are correlated with pathogenic events of
       HIV disease in man.
 DE    Animal  Flow Cytometry  Human  HIV/ISOLATION &
       PURIF/PHYSIOLOGY/*PATHOGENICITY  HIV Infections/*IMMUNOLOGY  Kinetics
       *Lymphocyte Depletion  Mice  Mice, SCID  T-Lymphocytes/*IMMUNOLOGY  T4
       Lymphocytes/IMMUNOLOGY  Virus Replication  MEETING ABSTRACT

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