OX40 and IL-7 play synergistic roles in the homeostatic proliferation of effector memory CD4+ T cells

Satoshi Yamaki, Shouji Ine, Takeshi Kawabe, Yuko Okuyama, Nobu Suzuki, Pejman Soroosh, Seyed Fazlollah Mousavi, Hiroyuki Nagashima, Shu Lan Sun, Takanori So, Takeshi Sasaki, Hideo Harigae, Kazuo Sugamura, Hironori Kudo, Motoshi Wada, Masaki Nio, Naoto Ishii

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


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+CD44highCD62Llow 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.

Original languageEnglish
Pages (from-to)3015-3025
Number of pages11
JournalEuropean Journal of Immunology
Issue number10
Publication statusPublished - 2014 Oct 1


  • Homeostatic proliferation
  • Memory CD4 T cells
  • OX40
  • Th17

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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