title: Quiescence-inducing and antiapoptotic activities of IL-15 enhance secondary CD4+ T cell responsiveness to antigen.
abstract: IL-15 shows functional redundancy with IL-2 due to its usage of the beta and gamma c subunit of the IL-2R. Yet, the requirement of IL-15 for an IL-15R alpha chain for high affinity interaction and the separate cellular sources of IL-2 and IL-15 suggest divergent activities for both cytokines. We compared the growth-inducing and proapoptotic or antiapoptotic activities of IL-15 and IL-2 on mature CD4+ T lymphocytes in the presence or absence of TCR occupancy. We found that the nature of IL-15 activity was critically dependent on the activation status of the T cells. In the absence of TCR triggering, IL-15 did not exert the growth factor activity of IL-2, but induced a quiescent phenotype, characterized by maintenance of the cells in the G0/G1 phase of the cell cycle and down-regulation of CD25, CD71, and CD95 expression. In the presence of appropriate TCR engagement, the IL-15-induced quiescent T cells were resistant against TCR-induced cell death and proliferated strongly. IL-2-treated cells, on the contrary, were sensitized to cell death, resulting in a negative feedback on cellular expansion and weak proliferative responsiveness. Consecutive action of IL-15 during the distinct phases of an in vitro immune response markedly increased the cell output of a second antigenic stimulation, as compared with IL-2. These results imply that during immune reactivity in vivo, IL-15 may take over from the transiently available IL-2 the role of survival factor but not of growth factor, hence promoting the long term maintenance of resting, Ag-experienced CD4+ T cells.
authors.affiliation: Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology, Ghent, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Dooms
authors.forename: M
authors.initials: M
authors.lastname: Desmedt
authors.forename: S
authors.initials: S
authors.lastname: Vancaeneghem
authors.forename: P
authors.initials: P
authors.lastname: Rottiers
authors.forename: V
authors.initials: V
authors.lastname: Goossens
authors.forename: W
authors.initials: W
authors.lastname: Fiers
authors.forename: J
authors.initials: J
authors.lastname: Grooten
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016923:Cell Death / Q000276:immunology; D002469:Cell Separation; D002999:Clone Cells; D004261:DNA Replication / Q000187:drug effects / Q000276:immunology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects; D007117:Immunization, Secondary; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D007399:Interphase / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D019409:Interleukin-15; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell