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Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-06-1644.
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Blood, 15 February 2003, Vol. 101, No. 4, pp. 1213-1219
PLENARY PAPER
Impact of simian immunodeficiency virus (SIV) infection on
lymphocyte numbers and T-cell turnover in different organs of rhesus
monkeys
Sieghart Sopper,
Dagmar Nierwetberg,
Astrid Halbach,
Ursula Sauer,
Carsten Scheller,
Christiane Stahl-Hennig,
Kerstin Mätz-Rensing,
Frank Schäfer,
Thomas Schneider,
Volker ter
Meulen, and
Justus G. Müller
From the Institut für Virologie und
Immunbiologie, Julius-Maximilians-Universität, Würzburg,
Germany; Deutsches Primatenzentrum, Göttingen,
Germany; Innere Medizin II, Universität des
Saarlandes, Homburg/Saar, Germany; and Institut für
Pathologie, Julius-Maximilians-Universität, Würzburg,
Germany.
HIV infection leads to reduced numbers and increased turnover of
CD4+ T cells in blood. However, blood represents only 2%
of the total lymphocyte pool, and information about other organs is
lacking, leading to controversy about the effects of HIV infection on
T-cell homeostasis. Therefore, we have determined phenotype and
turnover of lymphocyte subsets in various tissues of macaques.
Infection with simian immunodeficiency virus (SIV) resulted in
increased proliferation rates of T cells in all organs. Despite reduced CD4 counts in blood, absolute numbers of CD4+ T cells were
increased in spleen and lymph nodes and remained stable in nonlymphoid
organs such as liver, lung, bone marrow, and brain during the
asymptomatic phase, indicative for an altered tissue distribution. In
animals killed with first signs of AIDS, total body CD4 counts and
proliferation rates had returned to control levels, whereas thymocytes
were almost completely absent. Our data show that a drastically
increased turnover in the early stages of HIV infection, driven by a
generalized immune activation rather than a homeostatic response to
CD4+ T-cell destruction, is followed by exhaustion of the
regenerative capacity of the immune system.
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