title: Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates.
abstract: Interleukin-15 (IL-15) is a cytokine with potential therapeutic application in individuals with cancer or immunodeficiency to promote natural killer (NK)- and T-cell activation and proliferation or in vaccination protocols to generate long-lived memory T cells. Here we report that 10-50 μg/kg IL-15 administered intravenously daily for 12 days to rhesus macaques has both short- and long-lasting effects on T-cell homeostasis. Peripheral blood lymphopenia preceded a dramatic expansion of NK cells and memory CD8 T cells in the circulation, particularly a 4-fold expansion of central memory CD8 T cells and a 6-fold expansion of effector memory CD8 T cells. This expansion is a consequence of their activation in multiple tissues. A concomitant inverted CD4/CD8 T-cell ratio was observed throughout the body at day 13, a result of preferential CD8 expansion. Expanded T- and NK-cell populations declined in the blood soon after IL-15 was stopped, suggesting migration to extralymphoid sites. By day 48, homeostasis appears restored throughout the body, with the exception of the maintenance of an inverted CD4/CD8 ratio in lymph nodes. Thus, IL-15 generates a dramatic expansion of short-lived memory CD8 T cells and NK cells in immunocompetent macaques and has long-term effects on the balance of CD4(+) and CD8(+) T cells.
authors.affiliation: Immunotechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Enrico
authors.initials: E
authors.lastname: Lugli
authors.forename: Carolyn K
authors.initials: CK
authors.lastname: Goldman
authors.forename: Liyanage P
authors.initials: LP
authors.lastname: Perera
authors.forename: Jeremy
authors.initials: J
authors.lastname: Smedley
authors.forename: Rhonda
authors.initials: R
authors.lastname: Pung
authors.forename: Jason L
authors.initials: JL
authors.lastname: Yovandich
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Creekmore
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Waldmann
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000008:administration & dosage* / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D053699:Interleukin-7 Receptor alpha Subunit / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008253:Macaca mulatta; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; D019409:Interleukin-15; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D017452:Receptors, IgG; D011994:Recombinant Proteins