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M94A3227.TXT
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1994-10-25
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).