title: Evidence of a novel IL-2/15R beta-targeted cytokine involved in homeostatic proliferation of memory CD8+ T cells.
abstract: The homeostasis of memory CD8+ T cells is regulated by cytokines. IL-15 is shown to promote the proliferation of memory CD8+ T cells, while IL-2 suppresses their division in vivo. This inhibitory effect of IL-2 appears to occur indirectly, through other cell populations including CD25+CD4+ T cells; however, the details of this mechanism remain unclear. In this study, we show that 1) both Ag-experienced and memory phenotype CD8+ T cells divided after the depletion of IL-2 in vivo; 2) this division occurred normally and CD44(high)IL-2/15Rbeta(high) CD8+ T cells generated after IL-2 depletion in IL-15 knockout (KO) and in IL-7-depleted IL-15 KO mice; 3) surprisingly, the blockade of IL-2/15Rbeta signaling in IL-2-depleted IL-15 KO mice completely abolished the division of memory CD8+ T cells, although the only cytokines known to act through IL-2/15Rbeta are IL-2 and IL-15; and 4) the expression of IL-2/15Rbeta molecules on memory CD8+ T cells was required for their division induced by IL-2 depletion. These results demonstrate that the depletion of IL-2 in vivo induced memory CD8+ T cell division by an IL-15-independent but by an IL-2/15Rbeta-dependent mechanism, suggesting the existence of a novel IL-2/15Rbeta-utilizing cytokine that acts directly on memory CD8+ T cells to promote cell division.
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kamimura
authors.forename: Naoko
authors.initials: N
authors.lastname: Ueda
authors.forename: Yukihisa
authors.initials: Y
authors.lastname: Sawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Hachida
authors.forename: Toru
authors.initials: T
authors.lastname: Atsumi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Sawa
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Jin
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Suzuki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ishihara
authors.forename: Masaaki
authors.initials: M
authors.lastname: Murakami
authors.forename: Toshio
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007156:Immunologic Memory; D016130:Immunophenotyping; D019409:Interleukin-15 / Q000172:deficiency / Q000235:genetics; D007376:Interleukin-2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053646:Interleukin-2 Receptor beta Subunit; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005810:Multigene Family / Q000276:immunology; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D018960:Hyaluronan Receptors; C508022:Il2rb protein, mouse; D019409:Interleukin-15; D007376:Interleukin-2; D053646:Interleukin-2 Receptor beta Subunit; D018123:Receptors, Interleukin; D015375:Receptors, Interleukin-2