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Blood, 15 August 2000, Vol. 96, No. 4, pp. 1474-1479
IMMUNOBIOLOGY
Simian immunodeficiency virus-specific cytotoxic T lymphocytes
and cell-associated viral RNA levels in distinct lymphoid compartments
of SIVmac-infected rhesus monkeys
Marcelo J. Kuroda,
Jörn E. Schmitz,
Aruna Seth,
Ronald S. Veazey,
Christine E. Nickerson,
Michelle A. Lifton,
Peter J. Dailey,
Meryl A. Forman,
Paul Racz,
Klara Tenner-Racz, and
Norman L. Letvin
From the Division of Viral Pathogenesis, Department of
Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School,
Boston; the New England Regional Primate Research Center, Harvard
Medical School, Southborough, MA; Bayer Diagnostics, Nucleic Acid
Diagnostics, Emeryville, CA; Beckman Coulter, Miami, FL; and
Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.
Major histocompatibility class I-peptide tetramer technology and
simian immunodeficiency virus of macaques (SIVmac)-infected rhesus
monkeys were used to clarify the distribution of acquired immunodeficiency syndrome virus-specific cytotoxic T lymphocytes (CTL)
in secondary lymphoid organs and to assess the relationship between
these CTL and the extent of viral replication in the various anatomic
compartments. SIVmac Gag epitope-specific CD8+ T cells were
evaluated in the spleen, bone marrow, tonsils, thymus, and 5 different
lymph node compartments of 4 SIVmac-infected rhesus monkeys. The
average percentage of CD8+ T lymphocytes that bound this
tetramer in all the different lymph node compartments was similar to
that in peripheral blood lymphocytes in individual monkeys. The
percentage of CD8+ T cells that bound the tetramer in the
thymus was uniformly low in the monkeys. However, the percentage of
CD8+ T cells that bound the tetramer in bone marrow and
spleen was consistently higher than that seen in lymph nodes and
peripheral blood. The phenotypic profile of the tetramer-binding
CD8+ T lymphocytes in the different lymphoid compartments
was similar, showing a high expression of activation-associated
adhesion molecules and a low level expression of naive
T-cell-associated molecules. Surprisingly, no correlation was evident
between the percentage of tetramer-binding CD8+ T
lymphocytes and the magnitude of the cell-associated SIV RNA level in
each lymphoid compartment of individual monkeys. These studies suggest
that a dynamic process of trafficking may obscure the tendency of CTL
to localize in particular regional lymph nodes or that some lymphoid
organs may provide milieus that are particularly conducive to CTL expansion.
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