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Journal of Virology, April 2005, p. 4877-4885, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4877-4885.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Interleukin-15 Increases Effector Memory CD8+ T Cells and NK Cells in Simian Immunodeficiency Virus-Infected Macaques

Yvonne M. Mueller,1,{dagger} Constantinos Petrovas,1,{dagger} Paul M. Bojczuk,1 Ioannis D. Dimitriou,1 Brigitte Beer,2 Peter Silvera,2 Francois Villinger,3 J. Scott Cairns,4 Edward J. Gracely,5 Mark G. Lewis,6 and Peter D. Katsikis1*

Department of Microbiology and Immunology and Institute for Molecular Medicine and Infectious Disease,1 Family, Community, and Preventive Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania,5 Southern Research Institute, Frederick,2 BIOQUAL, Rockville, Maryland,6 Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia,3 Henry M. Jackson Foundation, Mercer Island, Washington4

Received 12 August 2004/ Accepted 19 November 2004

Interleukin-15 (IL-15) in vitro treatment of peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected individuals specifically enhances the function and survival of HIV-specific CD8+ T cells, while in vivo IL-15 treatment of mice preferentially expands memory CD8+ T cells. In this study, we investigated the in vivo effect of IL-15 treatment in 9 SIVmac251-infected cynomolgus macaques (low dose of IL-15, 10 µg/kg of body weight, n = 3; high dose of IL-15, 100 µg/kg, n = 3; control [saline], n = 3; dose administered twice weekly for 4 weeks). IL-15 treatment induced a nearly threefold increase in peripheral blood CD8+CD3– NK cells. Furthermore, CD8+ T-cell numbers increased more than twofold, mainly due to an increase in the CD45RA–CD62L– and CD45RA+CD62L– effector memory CD8+ T cells. Expression of Ki-67 in the CD8+ T cells indicated expansion of CD8+ T cells and not redistribution. IL-15 did not affect CD4+ T-cell, B-cell, and CD14+ macrophage numbers. No statistically significant differences in changes from baseline in the viral load were observed when control-, low-dose-, and high-dose-treated animals were compared. No clinical adverse effects were observed in any of the animals studied. The selective expansion of effector memory CD8+ T cells and NK cells by IL-15 further supports IL-15's possible therapeutic use in viral infections such as HIV infection.

* Corresponding author. Mailing address: Department of Microbiology and Immunology and Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 2900 Queen Ln., Philadelphia, PA 19129. Phone: (215) 991-8380. Fax: (215) 848-2271. E-mail: katsikis{at}drexel.edu.

{dagger} Y.M.M. and C.P. contributed equally to this study.

Journal of Virology, April 2005, p. 4877-4885, Vol. 79, No. 8
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.8.4877-4885.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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