title: OX40 and IL-7 play synergistic roles in the homeostatic proliferation of effector memory CD4⁺ T cells.
abstract: T-cell homeostasis preserves the numbers, the diversity and functional competence of different T-cell subsets that are required for adaptive immunity. Naïve CD4(+) T (TN ) cells are maintained in the periphery via the common γ-chain family cytokine IL-7 and weak antigenic signals. However, it is not clear how memory CD4(+) T-cell subsets are maintained in the periphery and which factors are responsible for the maintenance. To examine the homeostatic mechanisms, CFSE-labeled CD4(+) CD44(high) CD62L(low) effector memory T (TEM ) cells were transferred into sublethally-irradiated syngeneic C57BL/6 mice, and the systemic cell proliferative responses, which can be divided distinctively into fast and slow proliferations, were assessed by CFSE dye dilution. We found that the fast homeostatic proliferation of TEM cells was strictly regulated by both antigen and OX40 costimulatory signals and that the slow proliferation was dependent on IL-7. The simultaneous blockade of both OX40 and IL-7 signaling completely inhibited the both fast and slow proliferation. The antigen- and OX40-dependent fast proliferation preferentially expanded IL-17-producing helper T cells (Th17 cells). Thus, OX40 and IL-7 play synergistic, but distinct roles in the homeostatic proliferation of CD4(+) TEM cells.
authors.affiliation: Department of Microbiology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Pediatric Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaki
authors.forename: Shouji
authors.initials: S
authors.lastname: Ine
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawabe
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okuyama
authors.forename: Nobu
authors.initials: N
authors.lastname: Suzuki
authors.forename: Pejman
authors.initials: P
authors.lastname: Soroosh
authors.forename: Seyed Fazlollah
authors.initials: SF
authors.lastname: Mousavi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagashima
authors.forename: Shu-lan
authors.initials: SL
authors.lastname: Sun
authors.forename: Takanori
authors.initials: T
authors.lastname: So
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Hideo
authors.initials: H
authors.lastname: Harigae
authors.forename: Kazuo
authors.initials: K
authors.lastname: Sugamura
authors.forename: Hironori
authors.initials: H
authors.lastname: Kudo
authors.forename: Motoshi
authors.initials: M
authors.lastname: Wada
authors.forename: Masaki
authors.initials: M
authors.lastname: Nio
authors.forename: Naoto
authors.initials: N
authors.lastname: Ishii
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D005434:Flow Cytometry; D006706:Homeostasis / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D015851:Interleukin-7 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053262:Receptors, OX40 / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D015851:Interleukin-7; D053262:Receptors, OX40; C505717:Tnfrsf4 protein, mouse; C576410:interleukin-7, mouse
keywords: Homeostatic proliferation; Memory CD4+ T cells; OX40; Th17