title: Interleukin-15 increases effector memory CD8+ t cells and NK Cells in simian immunodeficiency virus-infected macaques.
abstract: 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 microg/kg of body weight, n = 3; high dose of IL-15, 100 microg/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.
authors.affiliation: Department of Microbiology and Immunology and Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 2900 Queen Ln., Philadelphia, PA 19129, USA.
authors.forename: Yvonne M
authors.initials: YM
authors.lastname: Mueller
authors.forename: Constantinos
authors.initials: C
authors.lastname: Petrovas
authors.forename: Paul M
authors.initials: PM
authors.lastname: Bojczuk
authors.forename: Ioannis D
authors.initials: ID
authors.lastname: Dimitriou
authors.forename: Brigitte
authors.initials: B
authors.lastname: Beer
authors.forename: Peter
authors.initials: P
authors.lastname: Silvera
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: J Scott
authors.initials: JS
authors.lastname: Cairns
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Gracely
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Peter D
authors.initials: PD
authors.lastname: Katsikis
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008252:Macaca fascicularis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*
chemical_list: D019409:Interleukin-15