title: Interleukin 15 is required for proliferative renewal of virus-specific memory CD8 T cells.
abstract: The generation and efficient maintenance of antigen-specific memory T cells is essential for long-lasting immunological protection. In this study, we examined the role of interleukin (IL)-15 in the generation and maintenance of virus-specific memory CD8 T cells using mice deficient in either IL-15 or the IL-15 receptor alpha chain. Both cytokine- and receptor-deficient mice made potent primary CD8 T cell responses to infection with lymphocytic choriomeningitis virus (LCMV), effectively cleared the virus and generated a pool of antigen-specific memory CD8 T cells that were phenotypically and functionally similar to memory CD8 T cells present in IL-15(+/+) mice. However, longitudinal analysis revealed a slow attrition of virus-specific memory CD8 T cells in the absence of IL-15 signals. This loss of CD8 T cells was due to a severe defect in the proliferative renewal of antigen-specific memory CD8 T cells in IL-15(-/-) mice. Taken together, these results show that IL-15 is not essential for the generation of memory CD8 T cells, but is required for homeostatic proliferation to maintain populations of memory cells over long periods of time.
authors.affiliation: Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Becker
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.forename: David
authors.initials: D
authors.lastname: Boone
authors.forename: Kaja
authors.initials: K
authors.lastname: Murali-Krishna
authors.forename: Rustom
authors.initials: R
authors.lastname: Antia
authors.forename: Averil
authors.initials: A
authors.lastname: Ma
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division / Q000502:physiology*; D005260:Female; D006706:Homeostasis / Q000502:physiology; D007156:Immunologic Memory / Q000502:physiology*; D019409:Interleukin-15 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014780:Viruses / Q000276:immunology*
chemical_list: D019409:Interleukin-15