Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates

Enrico Lugli, Carolyn K. Goldman, Liyanage P. Perera, Jeremy Smedley, Rhonda Pung, Jason L. Yovandich, Stephen P. Creekmore, Thomas A. Waldmann, Mario Roederer

Research output: Contribution to journalArticle

63 Citations (Scopus)

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 extra-lymphoid 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.

Original languageEnglish (US)
Pages (from-to)3238-3248
Number of pages11
JournalBlood
Volume116
Issue number17
DOIs
StatePublished - Oct 28 2010
Externally publishedYes

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Interleukin-15
T-cells
Lymphocytes
Primates
Homeostasis
T-Lymphocytes
Data storage equipment
Natural Killer T-Cells
Natural Killer Cells
Blood
Chemical activation
CD4-CD8 Ratio
Lymphopenia
Macaca
Macaca mulatta
Vaccination
Lymph Nodes
Maintenance
Cell Proliferation
Cytokines

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Lugli, E., Goldman, C. K., Perera, L. P., Smedley, J., Pung, R., Yovandich, J. L., ... Roederer, M. (2010). Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates. Blood, 116(17), 3238-3248. https://doi.org/10.1182/blood-2010-03-275438

Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates. / Lugli, Enrico; Goldman, Carolyn K.; Perera, Liyanage P.; Smedley, Jeremy; Pung, Rhonda; Yovandich, Jason L.; Creekmore, Stephen P.; Waldmann, Thomas A.; Roederer, Mario.

In: Blood, Vol. 116, No. 17, 28.10.2010, p. 3238-3248.

Research output: Contribution to journalArticle

Lugli, E, Goldman, CK, Perera, LP, Smedley, J, Pung, R, Yovandich, JL, Creekmore, SP, Waldmann, TA & Roederer, M 2010, 'Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates', Blood, vol. 116, no. 17, pp. 3238-3248. https://doi.org/10.1182/blood-2010-03-275438
Lugli, Enrico ; Goldman, Carolyn K. ; Perera, Liyanage P. ; Smedley, Jeremy ; Pung, Rhonda ; Yovandich, Jason L. ; Creekmore, Stephen P. ; Waldmann, Thomas A. ; Roederer, Mario. / Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates. In: Blood. 2010 ; Vol. 116, No. 17. pp. 3238-3248.
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