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IL-15 treatment during acute simian immunodeficiency virus (SIV) infection increases viral set point and accelerates disease progression despite the induction of stronger SIV-specific CD8+ T cell responses
Journal article   Open access   Peer reviewed

IL-15 treatment during acute simian immunodeficiency virus (SIV) infection increases viral set point and accelerates disease progression despite the induction of stronger SIV-specific CD8+ T cell responses

Yvonne M Mueller, Duc H Do, Susan R Altork, Carol M Artlett, Edward J Gracely, Christos D Katsetos, Agustin Legido, Francois Villinger, John D Altman, Charles R Brown, …
The Journal of immunology (1950), v 180(1), pp 350-360
01 Jan 2008
PMID: 18097036
url
https://doi.org/10.4049/jimmunol.180.1.350View
Published, Version of Record (VoR) Open

Abstract

Gene Products, gag - analysis Macaca mulatta Antibodies, Viral - blood Viral Load Meningoencephalitis - immunology CD4-Positive T-Lymphocytes - immunology Simian Acquired Immunodeficiency Syndrome - virology Leukocyte Common Antigens - analysis Killer Cells, Natural - immunology Disease Models, Animal Receptors, CCR5 - analysis Lymph Nodes - virology Lymph Nodes - immunology Disease Progression Simian Immunodeficiency Virus - physiology Interleukin-15 - pharmacology CD3 Complex - analysis Animals Ki-67 Antigen - analysis Simian Acquired Immunodeficiency Syndrome - immunology Viremia - virology Virus Replication Lymphocyte Activation - drug effects Meningoencephalitis - virology CD4 Antigens - analysis CD8-Positive T-Lymphocytes - drug effects Meningoencephalitis - pathology Viremia - immunology CD8-Positive T-Lymphocytes - immunology Simian Immunodeficiency Virus - drug effects
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.

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