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¹ Vaccine and Gene Therapy Institute, ² Department of Pathology, ³ Department of Molecular Microbiology and Immunology, and ⁴ Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006
⁵ AIDS and Cancer Virus Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD 21702
⁶ Seattle Biomedical Research Institute, Seattle, WA 98109
⁷ Yerkes National Primate Research Center and ⁸ Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322
⁹ Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02115

CORRESPONDENCE Louis J. Picker: pickerl{at}ohsu.edu

Depletion of CD8⁺ lymphocytes during acute simian immunodeficiency virus (SIV) infection of rhesus macaques (RMs) results in irreversible prolongation of peak-level viral replication and rapid disease progression, consistent with a major role for CD8⁺ lymphocytes in determining postacute-phase viral replication set points. However, we report that CD8⁺ lymphocyte depletion is also associated with a dramatic induction of proliferation among CD4⁺ effector memory T (T_EM) cells and, to a lesser extent, transitional memory T (T_TrM) cells, raising the question of whether an increased availability of optimal (activated/proliferating), CD4⁺/CCR5⁺ SIV "target" cells contributes to this accelerated pathogenesis. In keeping with this, depletion of CD8⁺ lymphocytes in SIV^– RMs led to a sustained increase in the number of potential CD4⁺ SIV targets, whereas such depletion in acute SIV infection led to increased target cell consumption. However, we found that the excess CD4⁺ T_EM cell proliferation of CD8⁺ lymphocyte–depleted, acutely SIV-infected RMs was completely inhibited by interleukin (IL)-15 neutralization, and that this inhibition did not abrogate the rapidly progressive infection in these RMs. Moreover, although administration of IL-15 during acute infection induced robust CD4⁺ T_EM and T_TrM cell proliferation, it did not recapitulate the viral dynamics of CD8⁺ lymphocyte depletion. These data suggest that CD8⁺ lymphocyte function has a larger impact on the outcome of acute SIV infection than the number and/or activation status of target cells available for infection and viral production.

© 2009 Okoye et al.
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This article has been cited by other articles:

• Mueller, Y. M., Do, D. H., Boyer, J. D., Kader, M., Mattapallil, J. J., Lewis, M. G., Weiner, D. B., Katsikis, P. D. (2009). CD8+ Cell Depletion of SHIV89.6P-Infected Macaques Induces CD4+ T Cell Proliferation that Contributes to Increased Viral Loads. J. Immunol. 183: 5006-5012 [Abstract] [Full Text]  

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