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* Department of Microbiology and Immunology, and Center for Immunology and Vaccine Science,
Department of Family, Community, and Preventive Medicine,
Departments of Pediatrics and Pathology and Laboratory Medicine, and
Departments of Pediatrics and Neurology, Drexel University College of Medicine, Philadelphia, PA 19129;
¶ Department of Pathology and Laboratory Medicine and
|| Emory Vaccine Research Center, Emory University School of Medicine, Atlanta, GA 30329;
# Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and
** Bioqual, Rockville, MD 20850
In this study, we examined the effect of in vivo treatment of acutely SIV-infected Mamu-A*01+ rhesus macaques with IL-15. IL-15 treatment during acute infection increased viral set point by 3 logs and accelerated the development of simian AIDS in two of six animals with one developing early minimal lesion SIV meningoencephalitis. Although IL-15 induced a 2- to 3-fold increase in SIV-specific CD8+ T cell and NK cell numbers at peak viremia and reduced lymph node (LN) SIV-infected cells, this had no impact on peak viremia and did not lower viral set point. At viral set point, however, activated SIV-specific CD8+ T cells and NK cells were reduced in the blood of IL-15-treated animals and LN SIV-infected cells were increased. Week 30 LN from IL-15-treated animals had significantly increased Gag-specific CD8+ T cell numbers, whereas total cell, lymphocyte, and CD4+ T cell numbers were reduced. IL-15 treatment significantly reduced anti-SIV Ab concentrations at week 3 and viral set point. IL-15 increased Ki-67+CD4+ T cells at week 1 of treatment and reduced blood CCR5+ and CD45RA–CD62L– CD4+ T cells. The frequency of day 7 Ki-67+CD4+ T cells strongly correlated with viral set point. These findings suggest that CD4+ T cell activation during acute infection determines subsequent viral set point and IL-15 treatment by increasing such activation elevates viral set point. Finally, IL-15-treated acutely SIV-infected primates may serve as a useful model to investigate the poorly understood mechanisms that control viral set point and disease progression in HIV infection.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grants R01 AI46719, AI52005, and AI62437 to P.D.K.
2 Address correspondence and reprint requests to Dr. Peter D. Katsikis, Department of Microbiology and Immunology, and Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129. E-mail address: Peter.Katsikis{at}DrexelMed.edu
3 Abbreviations used in this paper: LN, lymph node; AU, arbitrary unit.
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