Early Regeneration of Thymic Progenitors in Rhesus Macaques Infected with Simian Immunodeficiency Virus

doi:10.1084/jem.187.11.1767

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J. Exp. Med., Volume 187, Number 11, June 1, 1998 1767-1778

Early Regeneration of Thymic Progenitors in Rhesus Macaques Infected with Simian Immunodeficiency Virus

By Joanna J. Wykrzykowska,^* Michael Rosenzweig,^* Ronald S. Veazey,^* Meredith A. Simon,^* Katherine Halvorsen, Ronald C. Desrosiers,^* R. Paul Johnson,^* and Andrew A. Lackner^*

From the ^* New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772; and the Department of Mathematics, Smith College, Northampton, Massachusetts 01063

The thymus plays a critical role in the maturation and production of T lymphocytes and is a target of infection by human immunodeficiencyvirus (HIV) and the related simian immunodeficiency virus (SIV).Using the SIV/macaque model of AIDS, we examined the early effectsof SIV on the thymus. We found that thymic infection by SIV resultedin increased apoptosis 7-14 d after infection, followed by depletionof thymocyte progenitors by day 21. A marked rebound in thymocyteprogenitors occurred by day 50 and was accompanied by increasedlevels of cell proliferation in the thymus. Our results demonstratea marked increase in thymic progenitor activity very early inthe course of SIV infection, long before marked declines in peripheralCD4⁺ T cell counts.

Key words: AIDS; T cell homeostasis; apoptosis; animal model; pathogenesis

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